p53

In humans, the TP53 gene is located on the short arm of chromosome 17 (17p13.1). The gene spans 20 kb, with a non-coding exon 1 and a very long first intron of 10 kb, overlapping the Hp53int1 gene. The coding sequence contains five regions showing a high degree of conservation in vertebrates, predominantly in exons 2, 5, 6, 7 and 8, but the sequences found in invertebrates show only distant resemblance to mammalian TP53.{{cite journal | vauthors = May P, May E | title = Twenty years of p53 research: structural and functional aspects of the p53 protein | journal = Oncogene | volume = 18 | issue = 53 | pages = 7621–36 | date = December 1999 | pmid = 10618702 | doi = 10.1038/sj.onc.1203285 | doi-access = free }} TP53 orthologs{{cite web | title = OrthoMaM phylogenetic marker: TP53 coding sequence | url = http://www.orthomam.univ-montp2.fr/orthomam/data/cds/detailMarkers/ENSG00000141510_TP53.xml | access-date = 2009-12-02 | archive-url = https://web.archive.org/web/20180317110251/http://www.orthomam.univ-montp2.fr/orthomam/data/cds/detailMarkers/ENSG00000141510_TP53.xml | archive-date = 2018-03-17 | url-status = dead }} have been identified in most mammals for which complete genome data are available. Elephants, with 20 genes for TP53, rarely get cancer.{{cite journal | vauthors = Sulak M, Fong L, Mika K, Chigurupati S, Yon L, Mongan NP, Emes RD, Lynch VJ | title = TP53 copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants | journal = eLife | volume = 5 | date = September 2016 | pmid = 27642012 | doi = 10.7554/eLife.11994 | doi-access = free | pmc = 5061548 }}

In humans, a common polymorphism involves the substitution of an arginine for a proline at codon position 72 of exon 4. Many studies have investigated a genetic link between this variation and cancer susceptibility; however, the results have been controversial. For instance, a meta-analysis from 2009 failed to show a link for cervical cancer.{{cite journal | vauthors = Klug SJ, Ressing M, Koenig J, Abba MC, Agorastos T, Brenna SM, Ciotti M, Das BR, Del Mistro A, Dybikowska A, Giuliano AR, Gudleviciene Z, Gyllensten U, Haws AL, Helland A, Herrington CS, Hildesheim A, Humbey O, Jee SH, Kim JW, Madeleine MM, Menczer J, Ngan HY, Nishikawa A, Niwa Y, Pegoraro R, Pillai MR, Ranzani G, Rezza G, Rosenthal AN, Roychoudhury S, Saranath D, Schmitt VM, Sengupta S, Settheetham-Ishida W, Shirasawa H, Snijders PJ, Stoler MH, Suárez-Rincón AE, Szarka K, Tachezy R, Ueda M, van der Zee AG, von Knebel Doeberitz M, Wu MT, Yamashita T, Zehbe I, Blettner M | title = TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies | journal = The Lancet. Oncology | volume = 10 | issue = 8 | pages = 772–84 | date = August 2009 | pmid = 19625214 | doi = 10.1016/S1470-2045(09)70187-1 }} A 2011 study found that the TP53 proline mutation did have a profound effect on pancreatic cancer risk among males.{{cite journal | vauthors = Sonoyama T, Sakai A, Mita Y, Yasuda Y, Kawamoto H, Yagi T, Yoshioka M, Mimura T, Nakachi K, Ouchida M, Yamamoto K, Shimizu K | title = TP53 codon 72 polymorphism is associated with pancreatic cancer risk in males, smokers and drinkers | journal = Molecular Medicine Reports | volume = 4 | issue = 3 | pages = 489–95 | year = 2011 | pmid = 21468597 | doi = 10.3892/mmr.2011.449 | doi-access = free }} A study of Arab women found that proline homozygosity at TP53 codon 72 is associated with a decreased risk for breast cancer.{{cite journal | vauthors = Alawadi S, Ghabreau L, Alsaleh M, Abdulaziz Z, Rafeek M, Akil N, Alkhalaf M | title = P53 gene polymorphisms and breast cancer risk in Arab women | journal = Medical Oncology | volume = 28 | issue = 3 | pages = 709–15 | date = September 2011 | pmid = 20443084 | doi = 10.1007/s12032-010-9505-4 | s2cid = 207372095 }} One study suggested that TP53 codon 72 polymorphisms, MDM2 SNP309, and A2164G may collectively be associated with non-oropharyngeal cancer susceptibility and that MDM2 SNP309 in combination with TP53 codon 72 may accelerate the development of non-oropharyngeal cancer in women.{{cite journal | vauthors = Yu H, Huang YJ, Liu Z, Wang LE, Li G, Sturgis EM, Johnson DG, Wei Q | title = Effects of MDM2 promoter polymorphisms and p53 codon 72 polymorphism on risk and age at onset of squamous cell carcinoma of the head and neck | journal = Molecular Carcinogenesis | volume = 50 | issue = 9 | pages = 697–706 | date = September 2011 | pmid = 21656578 | pmc = 3142329 | doi = 10.1002/mc.20806 }} A 2011 study found that TP53 codon 72 polymorphism was associated with an increased risk of lung cancer.{{cite journal | vauthors = Piao JM, Kim HN, Song HR, Kweon SS, Choi JS, Yun WJ, Kim YC, Oh IJ, Kim KS, Shin MH | title = p53 codon 72 polymorphism and the risk of lung cancer in a Korean population | journal = Lung Cancer | volume = 73 | issue = 3 | pages = 264–7 | date = September 2011 | pmid = 21316118 | doi = 10.1016/j.lungcan.2010.12.017 }}

Meta-analyses from 2011 found no significant associations between TP53 codon 72 polymorphisms and both colorectal cancer risk{{cite journal | vauthors = Wang JJ, Zheng Y, Sun L, Wang L, Yu PB, Dong JH, Zhang L, Xu J, Shi W, Ren YC | title = TP53 codon 72 polymorphism and colorectal cancer susceptibility: a meta-analysis | journal = Molecular Biology Reports | volume = 38 | issue = 8 | pages = 4847–53 | date = November 2011 | pmid = 21140221 | doi = 10.1007/s11033-010-0619-8 | s2cid = 11730631 }} and endometrial cancer risk.{{cite journal | vauthors = Jiang DK, Yao L, Ren WH, Wang WZ, Peng B, Yu L | title = TP53 Arg72Pro polymorphism and endometrial cancer risk: a meta-analysis | journal = Medical Oncology | volume = 28 | issue = 4 | pages = 1129–35 | date = December 2011 | pmid = 20552298 | doi = 10.1007/s12032-010-9597-x | s2cid = 32990396 }} A 2011 study of a Brazilian birth cohort found an association between the non-mutant arginine TP53 and individuals without a family history of cancer.{{cite journal | vauthors = Thurow HS, Haack R, Hartwig FP, Oliveira IO, Dellagostin OA, Gigante DP, Horta BL, Collares T, Seixas FK | title = TP53 gene polymorphism: importance to cancer, ethnicity and birth weight in a Brazilian cohort | journal = Journal of Biosciences | volume = 36 | issue = 5 | pages = 823–31 | date = December 2011 | pmid = 22116280 | doi = 10.1007/s12038-011-9147-5 | s2cid = 23027087 }} Another 2011 study found that the p53 homozygous (Pro/Pro) genotype was associated with a significantly increased risk for renal cell carcinoma.{{cite journal | vauthors = Huang CY, Su CT, Chu JS, Huang SP, Pu YS, Yang HY, Chung CJ, Wu CC, Hsueh YM | title = The polymorphisms of P53 codon 72 and MDM2 SNP309 and renal cell carcinoma risk in a low arsenic exposure area | journal = Toxicology and Applied Pharmacology | volume = 257 | issue = 3 | pages = 349–55 | date = December 2011 | pmid = 21982800 | doi = 10.1016/j.taap.2011.09.018 | bibcode = 2011ToxAP.257..349H }}

File:P53 Schematic.tif

File:3KMD p53 DNABindingDomian.pngp53 has seven domains:

1. an acidic N-terminus transcription-activation domain (TAD), also known as activation domain 1 (AD1), which activates transcription factors. The N-terminus contains two complementary transcriptional activation domains, with a major one at residues 1–42 and a minor one at residues 55–75, specifically involved in the regulation of several pro-apoptotic genes.{{cite journal |vauthors=Venot C, Maratrat M, Dureuil C, Conseiller E, Bracco L, Debussche L |date=August 1998 |title=The requirement for the p53 proline-rich functional domain for mediation of apoptosis is correlated with specific PIG3 gene transactivation and with transcriptional repression |journal=The EMBO Journal |volume=17 |issue=16 |pages=4668–79 |doi=10.1093/emboj/17.16.4668 |pmc=1170796 |pmid=9707426}}
2. activation domain 2 (AD2) important for apoptotic activity: residues 43–63.
3. proline rich domain important for the apoptotic activity of p53 by nuclear exportation via MAPK: residues 64–92.
4. central DNA-binding core domain (DBD). Contains one zinc atom and several arginine amino acids: residues 102–292. This region is responsible for binding the p53 co-repressor LMO3.{{cite journal |vauthors=Larsen S, Yokochi T, Isogai E, Nakamura Y, Ozaki T, Nakagawara A |date=February 2010 |title=LMO3 interacts with p53 and inhibits its transcriptional activity |journal=Biochemical and Biophysical Research Communications |volume=392 |issue=3 |pages=252–7 |doi=10.1016/j.bbrc.2009.12.010 |pmid=19995558}}
5. Nuclear Localization Signaling (NLS) domain, residues 316–325.
6. homo-oligomerisation domain (OD): residues 307–355. Tetramerization is essential for the activity of p53 in vivo.
7. C-terminal involved in downregulation of DNA binding of the central domain: residues 356–393.{{cite journal |vauthors=Harms KL, Chen X |date=March 2005 |title=The C terminus of p53 family proteins is a cell fate determinant |journal=Molecular and Cellular Biology |volume=25 |issue=5 |pages=2014–30 |doi=10.1128/MCB.25.5.2014-2030.2005 |pmc=549381 |pmid=15713654}}

Mutations that deactivate p53 in cancer usually occur in the DBD. Most of these mutations destroy the ability of the protein to bind to its target DNA sequences, and thus prevents transcriptional activation of these genes. As such, mutations in the DBD are recessive loss-of-function mutations. Molecules of p53 with mutations in the OD dimerise with wild-type p53, and prevent them from activating transcription. Therefore, OD mutations have a dominant negative effect on the function of p53.

Wild-type p53 is a labile protein, comprising folded and unstructured regions that function in a synergistic manner.{{cite journal |vauthors=Bell S, Klein C, Müller L, Hansen S, Buchner J |date=October 2002 |title=p53 contains large unstructured regions in its native state |journal=Journal of Molecular Biology |volume=322 |issue=5 |pages=917–27 |doi=10.1016/S0022-2836(02)00848-3 |pmid=12367518}}

SDS-PAGE analysis indicates that p53 is a 53-kilodalton (kDa) protein. However, the actual mass of the full-length p53 protein (p53α) based on the sum of masses of the amino acid residues is only 43.7 kDa. This difference is due to the high number of proline residues in the protein, which slow its migration on SDS-PAGE, thus making it appear heavier than it actually is.{{cite journal |vauthors=Ziemer MA, Mason A, Carlson DM |date=September 1982 |title=Cell-free translations of proline-rich protein mRNAs |journal=The Journal of Biological Chemistry |volume=257 |issue=18 |pages=11176–80 |doi=10.1016/S0021-9258(18)33948-6 |pmid=7107651 |doi-access=free}}

p53 initially forms dimers cotranslationally during protein synthesis on ribosomes.{{cite journal | vauthors = Nicholls CD, McLure KG, Shields MA, Lee PW | title = Biogenesis of p53 involves cotranslational dimerization of monomers and posttranslational dimerization of dimers. Implications on the dominant negative effect | journal = The Journal of Biological Chemistry | volume = 277 | issue = 15 | pages = 12937–12945 | date = April 2002 | pmid = 11805092 | doi = 10.1074/jbc.M108815200 | doi-access = free }} Each dimer comprises two p53 monomers linked via their oligomerization domains.{{cite journal | vauthors = Suri V, Lanjuin A, Rosbash M | title = TIMELESS-dependent positive and negative autoregulation in the Drosophila circadian clock | journal = The EMBO Journal | volume = 18 | issue = 3 | pages = 675–686 | date = February 1999 | pmid = 9927427 | pmc = 1171160 | doi = 10.1093/emboj/18.3.675 }}

Dimers further associate posttranslationally into tetramers (a dimer of dimers).{{cite journal | vauthors = Nicholls CD, McLure KG, Shields MA, Lee PW | title = Biogenesis of p53 involves cotranslational dimerization of monomers and posttranslational dimerization of dimers. Implications on the dominant negative effect | journal = The Journal of Biological Chemistry | volume = 277 | issue = 15 | pages = 12937–12945 | date = April 2002 | pmid = 11805092 | doi = 10.1074/jbc.M108815200 | doi-access = free }}{{cite journal | vauthors = Natan E, Hirschberg D, Morgner N, Robinson CV, Fersht AR | title = Ultraslow oligomerization equilibria of p53 and its implications | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 34 | pages = 14327–14332 | date = August 2009 | pmid = 19667193 | pmc = 2731847 | doi = 10.1073/pnas.0907840106 | doi-access = free | bibcode = 2009PNAS..10614327N }} The tetramerization domain (residues 325–356) stabilizes this structure.{{cite journal | vauthors = Natan E, Hirschberg D, Morgner N, Robinson CV, Fersht AR | title = Ultraslow oligomerization equilibria of p53 and its implications | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 34 | pages = 14327–14332 | date = August 2009 | pmid = 19667193 | pmc = 2731847 | doi = 10.1073/pnas.0907840106 | doi-access = free | bibcode = 2009PNAS..10614327N }} Tetramers are the active form for DNA binding and transcriptional regulation.{{cite journal | vauthors = Ho WC, Fitzgerald MX, Marmorstein R | title = Structure of the p53 core domain dimer bound to DNA | journal = The Journal of Biological Chemistry | volume = 281 | issue = 29 | pages = 20494–20502 | date = July 2006 | pmid = 16717092 | doi = 10.1074/jbc.M603634200 | doi-access = free }}{{cite journal | vauthors = Suri V, Lanjuin A, Rosbash M | title = TIMELESS-dependent positive and negative autoregulation in the Drosophila circadian clock | journal = The EMBO Journal | volume = 18 | issue = 3 | pages = 675–686 | date = February 1999 | pmid = 9927427 | pmc = 1171160 | doi = 10.1093/emboj/18.3.675 }}

p53 plays a role in regulation or progression through the cell cycle, apoptosis, and genomic stability by means of several mechanisms:

• It can activate DNA repair proteins when DNA has sustained damage{{cite journal | vauthors = Janic A, Abad E, Amelio I | title = Decoding p53 tumor suppression: a crosstalk between genomic stability and epigenetic control? | journal = Cell Death and Differentiation | volume = 32 | issue = 1 | pages = 1–8 | date = January 2025 | pmid = 38379088 | pmc = 11742645 | doi = 10.1038/s41418-024-01259-9 | doi-access = free }}{{Creative Commons text attribution notice|cc=by4|from this source=yes}} Thus, it may be an important factor in aging.{{cite book | vauthors = Gilbert SF |title=Developmental Biology, 10th ed. |publisher=Sinauer Associates, Inc. Publishers |location=Sunderland, MA USA |pages=588}}
• It can arrest growth by holding the cell cycle at the G1/S regulation point on DNA damage recognition—if it holds the cell here for long enough, the DNA repair proteins will have time to fix the damage and the cell will be allowed to continue the cell cycle.
• It can initiate apoptosis (a form of programmed cell death) if DNA damage proves to be irreparable.
• It is essential for the senescence response to short telomeres.

File:P53 pathways.jpg

WAF1/CIP1 encodes for p21 and hundreds of other down-stream genes. p21 (WAF1) binds to the G1-S/CDK (CDK4/CDK6, CDK2, and CDK1) complexes (molecules important for the G1/S transition in the cell cycle) inhibiting their activity. {{cn|date=November 2024}}

When p21(WAF1) is complexed with CDK2, the cell cannot continue to the next stage of cell cycle. A mutant p53 will no longer bind DNA in an effective way, and, as a consequence, the p21 protein will not be available to act as the "stop signal" for cell division.{{cite book | chapter-url = https://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowSection&rid=gnd.section.107 | chapter = Skin and Connective Tissue | title = Genes and Disease |author=National Center for Biotechnology Information |publisher=United States National Institutes of Health |access-date=2008-05-28 |year=1998}} Studies of human embryonic stem cells (hESCs) commonly describe the nonfunctional p53-p21 axis of the G1/S checkpoint pathway with subsequent relevance for cell cycle regulation and the DNA damage response (DDR). Importantly, p21 mRNA is clearly present and upregulated after the DDR in hESCs, but p21 protein is not detectable. In this cell type, p53 activates numerous microRNAs (like miR-302a, miR-302b, miR-302c, and miR-302d) that directly inhibit the p21 expression in hESCs. {{cn|date=November 2024}}

The p21 protein binds directly to cyclin-CDK complexes that drive forward the cell cycle and inhibits their kinase activity, thereby causing cell cycle arrest to allow repair to take place. p21 can also mediate growth arrest associated with differentiation and a more permanent growth arrest associated with cellular senescence. The p21 gene contains several p53 response elements that mediate direct binding of the p53 protein, resulting in transcriptional activation of the gene encoding the p21 protein. {{cn|date=November 2024}}

[[File:Activation of p53 in response to stress signals initiates its transcriptional activity, leading to the activation of cellular protective pathways.jpg|thumb|Activation of p53 in response to stress signals initiates its transcriptional activity, leading to the activation of cellular protective pathways

p53 binds to the DNA in a tetrameric configuration and promotes the transcription of a wide array of genes. Pictured are key p53 pathways and transcriptional targets regulated by p53 with a specific emphasis on p53-dependent DNA repair genes. BER (base excision repair), NER (nucleotide excision repair), MMR (mismatch repair), HR (homologous recombination), NHEJ (non-homologous end-joining), DDR (DNA damage repair)]]

The p53 and RB1 pathways are linked via p14ARF, raising the possibility that the pathways may regulate each other.{{cite journal |vauthors=Bates S, Phillips AC, Clark PA, Stott F, Peters G, Ludwig RL, Vousden KH |title=p14ARF links the tumour suppressors RB and p53 |journal=Nature |volume=395 |issue=6698 |pages=124–5 |date=September 1998 |pmid=9744267 |doi=10.1038/25867 |bibcode=1998Natur.395..124B |s2cid=4355786}}

p53 expression can be stimulated by UV light, which also causes DNA damage. In this case, p53 can initiate events leading to tanning.{{cite magazine |title=Genome's guardian gets a tan started |url=https://www.newscientist.com/channel/health/mg19325955.800-genomes-guardian-gets-a-tan-started.html |magazine=New Scientist |date=March 17, 2007 |access-date=2007-03-29}}{{cite journal |vauthors=Cui R, Widlund HR, Feige E, Lin JY, Wilensky DL, Igras VE, D'Orazio J, Fung CY, Schanbacher CF, Granter SR, Fisher DE |title=Central role of p53 in the suntan response and pathologic hyperpigmentation |journal=Cell |volume=128 |issue=5 |pages=853–64 |date=March 2007 |pmid=17350573 |doi=10.1016/j.cell.2006.12.045 |doi-access=free}}

Levels of p53 play an important role in the maintenance of stem cells throughout development and the rest of human life.{{Cite journal|title=Functions of p53 in pluripotent stem cells|journal=Oxford Academic|date=2020 |volume=11|pages=71–78|doi=10.1007/s13238-019-00665-x |pmid=31691903 | vauthors = Fu X, Wu S, Li B, Xu Y, Liu J |issue=1 |pmc=6949194}}

In human embryonic stem cells (hESCs)s, p53 is maintained at low inactive levels.{{cite journal |vauthors=Jain AK, Allton K, Iacovino M, Mahen E, Milczarek RJ, Zwaka TP, Kyba M, Barton MC |title=p53 regulates cell cycle and microRNAs to promote differentiation of human embryonic stem cells |journal=PLOS Biology |volume=10 |issue=2 |pages= e1001268 |pmid=22389628 |pmc=3289600 |doi=10.1371/journal.pbio.1001268 |year=2012 |doi-access=free }} This is because activation of p53 leads to rapid differentiation of hESCs.{{cite journal |vauthors=Maimets T, Neganova I, Armstrong L, Lako M |title=Activation of p53 by nutlin leads to rapid differentiation of human embryonic stem cells |journal=Oncogene |volume=27 |issue=40 |pages=5277–87 |date=September 2008 |pmid=18521083 |doi=10.1038/onc.2008.166 |doi-access=free}} Studies have shown that knocking out p53 delays differentiation and that adding p53 causes spontaneous differentiation, showing how p53 promotes differentiation of hESCs and plays a key role in cell cycle as a differentiation regulator. When p53 becomes stabilized and activated in hESCs, it increases p21 to establish a longer G1. This typically leads to abolition of S-phase entry, which stops the cell cycle in G1, leading to differentiation. Work in mouse embryonic stem cells has recently shown however that the expression of P53 does not necessarily lead to differentiation.{{cite journal |vauthors=ter Huurne M, Peng T, Yi G, van Mierlo G, Marks H, Stunnenberg HG |title=Critical role for P53 in regulating the cell cycle of ground state embryonic stem cells |journal=Stem Cell Reports |volume=14 |issue=2 |pages=175–183 |date=February 2020 |pmid=32004494 |doi=10.1016/j.stemcr.2020.01.001 |doi-access=free |pmc=7013234}} p53 also activates miR-34a and miR-145, which then repress the hESCs pluripotency factors, further instigating differentiation.

In adult stem cells, p53 regulation is important for maintenance of stemness in adult stem cell niches. Mechanical signals such as hypoxia affect levels of p53 in these niche cells through the hypoxia inducible factors, HIF-1α and HIF-2α. While HIF-1α stabilizes p53, HIF-2α suppresses it.{{cite journal |vauthors=Das B, Bayat-Mokhtari R, Tsui M, Lotfi S, Tsuchida R, Felsher DW, Yeger H |title=HIF-2α suppresses p53 to enhance the stemness and regenerative potential of human embryonic stem cells |journal=Stem Cells |volume=30 |issue=8 |pages=1685–95 |date=August 2012 |pmid=22689594 |pmc=3584519 |doi=10.1002/stem.1142}} Suppression of p53 plays important roles in cancer stem cell phenotype, induced pluripotent stem cells and other stem cell roles and behaviors, such as blastema formation. Cells with decreased levels of p53 have been shown to reprogram into stem cells with a much greater efficiency than normal cells.{{cite journal |vauthors=Lake BB, Fink J, Klemetsaune L, Fu X, Jeffers JR, Zambetti GP, Xu Y |title=Context-dependent enhancement of induced pluripotent stem cell reprogramming by silencing Puma |journal=Stem Cells |volume=30 |issue=5 |pages=888–97 |date=May 2012 |pmid=22311782 |pmc=3531606 |doi=10.1002/stem.1054}}{{cite journal |vauthors=Marión RM, Strati K, Li H, Murga M, Blanco R, Ortega S, Fernandez-Capetillo O, Serrano M, Blasco MA |title=A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity |journal=Nature |volume=460 |issue=7259 |pages=1149–53 |date=August 2009 |pmid=19668189 |pmc=3624089 |doi=10.1038/nature08287 |bibcode=2009Natur.460.1149M}} Papers suggest that the lack of cell cycle arrest and apoptosis gives more cells the chance to be reprogrammed. Decreased levels of p53 were also shown to be a crucial aspect of blastema formation in the legs of salamanders.{{cite journal |vauthors=Yun MH, Gates PB, Brockes JP |title=Regulation of p53 is critical for vertebrate limb regeneration |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=110 |issue=43 |pages=17392–7 |date=October 2013 |pmid=24101460 |pmc=3808590 |doi=10.1073/pnas.1310519110 |bibcode=2013PNAS..11017392Y |doi-access=free}} p53 regulation is very important in acting as a barrier between stem cells and a differentiated stem cell state, as well as a barrier between stem cells being functional and being cancerous.{{cite journal |vauthors=Aloni-Grinstein R, Shetzer Y, Kaufman T, Rotter V |title=p53: the barrier to cancer stem cell formation |journal=FEBS Letters |volume=588 |issue=16 |pages=2580–9 |date=August 2014 |pmid=24560790 |doi=10.1016/j.febslet.2014.02.011 |s2cid=37901173 |doi-access=free|bibcode=2014FEBSL.588.2580A }}

File:P53 and angiogenesis.png

Apart from the cellular and molecular effects above, p53 has a tissue-level anticancer effect that works by inhibiting angiogenesis. As tumors grow they need to recruit new blood vessels to supply them, and p53 inhibits that by (i) interfering with regulators of tumor hypoxia that also affect angiogenesis, such as HIF1 and HIF2, (ii) inhibiting the production of angiogenic promoting factors, and (iii) directly increasing the production of angiogenesis inhibitors, such as arresten.{{cite journal | vauthors = Teodoro JG, Evans SK, Green MR | title = Inhibition of tumor angiogenesis by p53: a new role for the guardian of the genome | journal = Journal of Molecular Medicine | volume = 85 | issue = 11 | pages = 1175–1186 | date = November 2007 | pmid = 17589818 | doi = 10.1007/s00109-007-0221-2 | type = Review | s2cid = 10094554 }}{{cite journal | vauthors = Assadian S, El-Assaad W, Wang XQ, Gannon PO, Barrès V, Latour M, Mes-Masson AM, Saad F, Sado Y, Dostie J, Teodoro JG | title = p53 inhibits angiogenesis by inducing the production of Arresten | journal = Cancer Research | volume = 72 | issue = 5 | pages = 1270–1279 | date = March 2012 | pmid = 22253229 | doi = 10.1158/0008-5472.CAN-11-2348 | doi-access = free }}

p53 by regulating Leukemia Inhibitory Factor has been shown to facilitate implantation in the mouse and possibly human reproduction.{{cite journal | vauthors = Hu W, Feng Z, Teresky AK, Levine AJ | title = p53 regulates maternal reproduction through LIF | journal = Nature | volume = 450 | issue = 7170 | pages = 721–4 | date = November 2007 | pmid = 18046411 | doi = 10.1038/nature05993 | bibcode = 2007Natur.450..721H | s2cid = 4357527 }}

The immune response to infection also involves p53 and NF-κB. Checkpoint control of the cell cycle and of apoptosis by p53 is inhibited by some infections such as Mycoplasma bacteria,{{cite journal | vauthors = Borchsenius SN, Daks A, Fedorova O, Chernova O, Barlev NA | title = Effects of mycoplasma infection on the host organism response via p53/NF-κB signaling | journal = Journal of Cellular Physiology | volume = 234 | issue = 1 | pages = 171–180 | date = January 2018 | pmid = 30146800 | doi = 10.1002/jcp.26781 }} raising the specter of oncogenic infection.

p53 acts as a cellular stress sensor. It is normally kept at low levels by being constantly marked for degradation by the E3 ubiquitin ligase protein MDM2.{{cite journal | vauthors = Bykov VJ, Eriksson SE, Bianchi J, Wiman KG | title = Targeting mutant p53 for efficient cancer therapy | journal = Nature Reviews. Cancer | volume = 18 | issue = 2 | pages = 89–102 | date = February 2018 | pmid = 29242642 | doi = 10.1038/nrc.2017.109 | s2cid = 4552678 }} p53 is activated in response to myriad stressors – including DNA damage (induced by either UV, IR, or chemical agents such as hydrogen peroxide), oxidative stress,{{cite journal | vauthors = Han ES, Muller FL, Pérez VI, Qi W, Liang H, Xi L, Fu C, Doyle E, Hickey M, Cornell J, Epstein CJ, Roberts LJ, Van Remmen H, Richardson A | title = The in vivo gene expression signature of oxidative stress | journal = Physiological Genomics | volume = 34 | issue = 1 | pages = 112–126 | date = June 2008 | pmid = 18445702 | pmc = 2532791 | doi = 10.1152/physiolgenomics.00239.2007 }} osmotic shock, ribonucleotide depletion, viral lung infections{{cite journal | vauthors = Grajales-Reyes GE, Colonna M | title = Interferon responses in viral pneumonias | journal = Science | volume = 369 | issue = 6504 | pages = 626–627 | date = August 2020 | pmid = 32764056 | doi = 10.1126/science.abd2208 | bibcode = 2020Sci...369..626G }} and deregulated oncogene expression. This activation is marked by two major events. First, the half-life of the p53 protein is increased drastically, leading to a quick accumulation of p53 in stressed cells. Second, a conformational change forces p53 to be activated as a transcription regulator in these cells. The critical event leading to the activation of p53 is the phosphorylation of its N-terminal domain. The N-terminal transcriptional activation domain contains a large number of phosphorylation sites and can be considered as the primary target for protein kinases transducing stress signals. {{cn|date=November 2024}}

The protein kinases that are known to target this transcriptional activation domain of p53 can be roughly divided into two groups. A first group of protein kinases belongs to the MAPK family (JNK1-3, ERK1-2, p38 MAPK), which is known to respond to several types of stress, such as membrane damage, oxidative stress, osmotic shock, heat shock, etc. A second group of protein kinases (ATR, ATM, CHK1 and CHK2, DNA-PK, CAK, TP53RK) is implicated in the genome integrity checkpoint, a molecular cascade that detects and responds to several forms of DNA damage caused by genotoxic stress. Oncogenes also stimulate p53 activation, mediated by the protein p14ARF. {{cn|date=November 2024}}

In unstressed cells, p53 levels are kept low through a continuous degradation of p53. A protein called Mdm2 (also called HDM2 in humans), binds to p53, preventing its action and transports it from the nucleus to the cytosol. Mdm2 also acts as an ubiquitin ligase and covalently attaches ubiquitin to p53 and thus marks p53 for degradation by the proteasome. However, ubiquitylation of p53 is reversible. On activation of p53, Mdm2 is also activated, setting up a feedback loop. p53 levels can show oscillations (or repeated pulses) in response to certain stresses, and these pulses can be important in determining whether the cells survive the stress, or die.{{cite journal | vauthors = Purvis JE, Karhohs KW, Mock C, Batchelor E, Loewer A, Lahav G | title = p53 dynamics control cell fate | journal = Science | volume = 336 | issue = 6087 | pages = 1440–1444 | date = June 2012 | pmid = 22700930 | pmc = 4162876 | doi = 10.1126/science.1218351 | bibcode = 2012Sci...336.1440P }}

MI-63 binds to MDM2, reactivating p53 in situations where p53's function has become inhibited.{{cite journal | vauthors = Canner JA, Sobo M, Ball S, Hutzen B, DeAngelis S, Willis W, Studebaker AW, Ding K, Wang S, Yang D, Lin J | title = MI-63: a novel small-molecule inhibitor targets MDM2 and induces apoptosis in embryonal and alveolar rhabdomyosarcoma cells with wild-type p53 | journal = British Journal of Cancer | volume = 101 | issue = 5 | pages = 774–81 | date = September 2009 | pmid = 19707204 | pmc = 2736841 | doi = 10.1038/sj.bjc.6605199 }}

A ubiquitin specific protease, USP7 (or HAUSP), can cleave ubiquitin off p53, thereby protecting it from proteasome-dependent degradation via the ubiquitin ligase pathway. This is one means by which p53 is stabilized in response to oncogenic insults. USP42 has also been shown to deubiquitinate p53 and may be required for the ability of p53 to respond to stress.{{cite journal | vauthors = Hock AK, Vigneron AM, Carter S, Ludwig RL, Vousden KH | title = Regulation of p53 stability and function by the deubiquitinating enzyme USP42 | journal = The EMBO Journal | volume = 30 | issue = 24 | pages = 4921–30 | date = November 2011 | pmid = 22085928 | pmc = 3243628 | doi = 10.1038/emboj.2011.419 }}

Recent research has shown that HAUSP is mainly localized in the nucleus, though a fraction of it can be found in the cytoplasm and mitochondria. Overexpression of HAUSP results in p53 stabilization. However, depletion of HAUSP does not result in a decrease in p53 levels but rather increases p53 levels due to the fact that HAUSP binds and deubiquitinates Mdm2. It has been shown that HAUSP is a better binding partner to Mdm2 than p53 in unstressed cells.

USP10, however, has been shown to be located in the cytoplasm in unstressed cells and deubiquitinates cytoplasmic p53, reversing Mdm2 ubiquitination. Following DNA damage, USP10 translocates to the nucleus and contributes to p53 stability. Also USP10 does not interact with Mdm2.

Phosphorylation of the N-terminal end of p53 by the above-mentioned protein kinases disrupts Mdm2-binding. Other proteins, such as Pin1, are then recruited to p53 and induce a conformational change in p53, which prevents Mdm2-binding even more. Phosphorylation also allows for binding of transcriptional coactivators, like p300 and PCAF, which then acetylate the C-terminal end of p53, exposing the DNA binding domain of p53, allowing it to activate or repress specific genes. Deacetylase enzymes, such as Sirt1 and Sirt7, can deacetylate p53, leading to an inhibition of apoptosis.{{cite journal | vauthors = Vakhrusheva O, Smolka C, Gajawada P, Kostin S, Boettger T, Kubin T, Braun T, Bober E | title = Sirt7 increases stress resistance of cardiomyocytes and prevents apoptosis and inflammatory cardiomyopathy in mice | journal = Circulation Research | volume = 102 | issue = 6 | pages = 703–10 | date = March 2008 | pmid = 18239138 | doi = 10.1161/CIRCRESAHA.107.164558 | doi-access = free }} Some oncogenes can also stimulate the transcription of proteins that bind to MDM2 and inhibit its activity. {{cn|date=November 2024}}

Epigenetic marks like histone methylation can also regulate p53, for example, p53 interacts directly with a repressive Trim24 cofactor that binds histones in regions of the genome that are epigenetically repressed.{{cite journal | vauthors = Isbel L, Iskar M, Durdu S, Grand RS, Weiss J, Hietter-Pfeiffer E, Kozicka Z, Michael AK, Burger L, Thomä NH, Schübeler D | title = Readout of histone methylation by Trim24 locally restricts chromatin opening by p53 | journal = Nature Structural & Molecular Biology | volume = 30 | issue = 7 | pages = 948–57 | date = June 2023 | pmid = 37386214 | doi = 10.1038/s41594-023-01021-8| doi-access = free | pmc = 10352137 | hdl = 2440/139184 | hdl-access = free }} Trim24 prevents p53 from activating its targets, but only in these regions, effectively giving p53 the ability to 'read out' the histone profile at key target genes and act in a gene-specific manner. {{cn|date=November 2024}}

File:Signal transduction pathways.svg]]

File:Anaplastic astrocytoma - p53 - very high mag.jpg showing cells with abnormal p53 expression (brown) in a brain tumor. p53 immunostain.]]

If the TP53 gene is damaged, tumor suppression is severely compromised. People who inherit only one functional copy of the TP53 gene will most likely develop tumors in early adulthood, a disorder known as Li–Fraumeni syndrome. {{cn|date=November 2024}}

The TP53 gene can also be modified by mutagens (chemicals, radiation, or viruses), increasing the likelihood for uncontrolled cell division. More than 50 percent of human tumors contain a mutation or deletion of the TP53 gene.{{cite journal | vauthors = Hollstein M, Sidransky D, Vogelstein B, Harris CC | title = p53 mutations in human cancers | journal = Science | volume = 253 | issue = 5015 | pages = 49–53 | date = July 1991 | pmid = 1905840 | doi = 10.1126/science.1905840 | bibcode = 1991Sci...253...49H | s2cid = 38527914 | url = https://zenodo.org/record/1230948 }} Loss of p53 creates genomic instability that most often results in an aneuploidy phenotype.{{cite journal | vauthors = Schmitt CA, Fridman JS, Yang M, Baranov E, Hoffman RM, Lowe SW | title = Dissecting p53 tumor suppressor functions in vivo | journal = Cancer Cell | volume = 1 | issue = 3 | pages = 289–98 | date = April 2002 | pmid = 12086865 | doi = 10.1016/S1535-6108(02)00047-8 | doi-access = free }}

Increasing the amount of p53 may seem a solution for treatment of tumors or prevention of their spreading. This, however, is not a usable method of treatment, since it can cause premature aging.{{cite journal | vauthors = Tyner SD, Venkatachalam S, Choi J, Jones S, Ghebranious N, Igelmann H, Lu X, Soron G, Cooper B, Brayton C, Park SH, Thompson T, Karsenty G, Bradley A, Donehower LA | title = p53 mutant mice that display early ageing-associated phenotypes | journal = Nature | volume = 415 | issue = 6867 | pages = 45–53 | date = January 2002 | pmid = 11780111 | doi = 10.1038/415045a | bibcode = 2002Natur.415...45T | s2cid = 749047 }} Restoring endogenous normal p53 function holds some promise. Research has shown that this restoration can lead to regression of certain cancer cells without damaging other cells in the process. The ways by which tumor regression occurs depends mainly on the tumor type. For example, restoration of endogenous p53 function in lymphomas may induce apoptosis, while cell growth may be reduced to normal levels. Thus, pharmacological reactivation of p53 presents itself as a viable cancer treatment option.{{cite journal | vauthors = Ventura A, Kirsch DG, McLaughlin ME, Tuveson DA, Grimm J, Lintault L, Newman J, Reczek EE, Weissleder R, Jacks T | title = Restoration of p53 function leads to tumour regression in vivo | journal = Nature | volume = 445 | issue = 7128 | pages = 661–5 | date = February 2007 | pmid = 17251932 | doi = 10.1038/nature05541 | s2cid = 4373520 }}{{cite journal | vauthors = Herce HD, Deng W, Helma J, Leonhardt H, Cardoso MC | title = Visualization and targeted disruption of protein interactions in living cells | journal = Nature Communications | volume = 4 | pages = 2660 | year = 2013 | pmid = 24154492 | pmc = 3826628 | doi = 10.1038/ncomms3660 | bibcode = 2013NatCo...4.2660H }} The first commercial gene therapy, Gendicine, was approved in China in 2003 for the treatment of head and neck squamous cell carcinoma. It delivers a functional copy of the p53 gene using an engineered adenovirus.{{cite journal | vauthors = Pearson S, Jia H, Kandachi K | title = China approves first gene therapy | journal = Nature Biotechnology | volume = 22 | issue = 1 | pages = 3–4 | date = January 2004 | pmid = 14704685 | doi = 10.1038/nbt0104-3 | pmc = 7097065 }}

Certain pathogens can also affect the p53 protein that the TP53 gene expresses. One such example, human papillomavirus (HPV), encodes a protein, E6, which binds to the p53 protein and inactivates it. This mechanism, in synergy with the inactivation of the cell cycle regulator pRb by the HPV protein E7, allows for repeated cell division manifested clinically as warts. Certain HPV types, in particular types 16 and 18, can also lead to progression from a benign wart to low or high-grade cervical dysplasia, which are reversible forms of precancerous lesions. Persistent infection of the cervix over the years can cause irreversible changes leading to carcinoma in situ and eventually invasive cervical cancer. This results from the effects of HPV genes, particularly those encoding E6 and E7, which are the two viral oncoproteins that are preferentially retained and expressed in cervical cancers by integration of the viral DNA into the host genome.{{cite book | vauthors = Angeletti PC, Zhang L, Wood C | chapter = The Viral Etiology of AIDS-Associated Malignancies | title = HIV-1: Molecular Biology and Pathogenesis | series = Advances in Pharmacology | volume = 56 | pages = 509–57 | year = 2008 | pmid = 18086422 | pmc = 2149907 | doi = 10.1016/S1054-3589(07)56016-3 | isbn = 978-0-12-373601-7 }}

The p53 protein is continually produced and degraded in cells of healthy people, resulting in damped oscillation (see a stochastic model of this process in {{cite journal | vauthors = Ribeiro AS, Charlebois DA, Lloyd-Price J | title = CellLine, a stochastic cell lineage simulator | journal = Bioinformatics | volume = 23 | issue = 24 | pages = 3409–3411 | date = December 2007 | pmid = 17928303 | doi = 10.1093/bioinformatics/btm491 | doi-access = free }}). The degradation of the p53 protein is associated with binding of MDM2. In a negative feedback loop, MDM2 itself is induced by the p53 protein. Mutant p53 proteins often fail to induce MDM2, causing p53 to accumulate at very high levels. Moreover, the mutant p53 protein itself can inhibit normal p53 protein levels. In some cases, single missense mutations in p53 have been shown to disrupt p53 stability and function.{{cite journal | vauthors = Bullock AN, Henckel J, DeDecker BS, Johnson CM, Nikolova PV, Proctor MR, Lane DP, Fersht AR | title = Thermodynamic stability of wild-type and mutant p53 core domain | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 26 | pages = 14338–42 | date = December 1997 | pmid = 9405613 | pmc = 24967 | doi = 10.1073/pnas.94.26.14338 | bibcode = 1997PNAS...9414338B | doi-access = free }}

File:Expression of p53 in urothelial neoplasms.png for p53 can help distinguish a papillary urothelial neoplasm of low malignant potential (PUNLMP) from a low grade urothelial carcinoma. Overexpression is seen in 75% of low-grade urothelial carcinomas and only 10% of PUNLMP.Image is taken from following source, with some modification by Mikael Häggström, MD:
- {{cite journal| vauthors =Schallenberg S, Plage H, Hofbauer S, Furlano K, Weinberger S, Bruch PG | title=Altered p53/p16 expression is linked to urothelial carcinoma progression but largely unrelated to prognosis in muscle-invasive tumors. | journal=Acta Oncol | year= 2023 | volume= 62| issue= 12| pages= 1880–1889 | pmid=37938166 | doi=10.1080/0284186X.2023.2277344 | pmc= | doi-access=free }} Source for role in distinguishing PUNLMP from low-grade carcinoma:
- {{cite journal| author=Kalantari MR, Ahmadnia H| title=P53 overexpression in bladder urothelial neoplasms: new aspect of World Health Organization/International Society of Urological Pathology classification. | journal=Urol J | year= 2007 | volume= 4 | issue= 4 | pages= 230–3 | pmid=18270948 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18270948 }} ]]

Suppression of p53 in human breast cancer cells is shown to lead to increased CXCR5 chemokine receptor gene expression and activated cell migration in response to chemokine CXCL13.{{cite journal | vauthors = Mitkin NA, Hook CD, Schwartz AM, Biswas S, Kochetkov DV, Muratova AM, Afanasyeva MA, Kravchenko JE, Bhattacharyya A, Kuprash DV | title = p53-dependent expression of CXCR5 chemokine receptor in MCF-7 breast cancer cells | journal = Scientific Reports | volume = 5 | issue = 5 | pages = 9330 | date = March 2015 | pmid = 25786345 | pmc = 4365401 | doi = 10.1038/srep09330 | bibcode = 2015NatSR...5.9330M }}

One study found that p53 and Myc proteins were key to the survival of Chronic Myeloid Leukaemia (CML) cells. Targeting p53 and Myc proteins with drugs gave positive results on mice with CML.{{cite journal | vauthors = Abraham SA, Hopcroft LE, Carrick E, Drotar ME, Dunn K, Williamson AJ, Korfi K, Baquero P, Park LE, Scott MT, Pellicano F, Pierce A, Copland M, Nourse C, Grimmond SM, Vetrie D, Whetton AD, Holyoake TL | title = Dual targeting of p53 and c-MYC selectively eliminates leukaemic stem cells | journal = Nature | volume = 534 | issue = 7607 | pages = 341–6 | date = June 2016 | pmid = 27281222 | pmc = 4913876 | doi = 10.1038/nature18288 | bibcode = 2016Natur.534..341A }}{{Cite news |url=https://www.myscience.uk/news/2016/cientists_identify_drugs_to_target_achilles_heel_of_chronic_myeloid_leukaemia_cells-2016-glasgow |title=Scientists identify drugs to target 'Achilles heel' of Chronic Myeloid Leukaemia cells |date=2016-06-08 |website=myScience |access-date=2016-06-09}}

Most p53 mutations are detected by DNA sequencing. However, it is known that single missense mutations can have a large spectrum from rather mild to very severe functional effects.

File:P53 mutant.jpg

The large spectrum of cancer phenotypes due to mutations in the TP53 gene is also supported by the fact that different isoforms of p53 proteins have different cellular mechanisms for prevention against cancer. Mutations in TP53 can give rise to different isoforms, preventing their overall functionality in different cellular mechanisms and thereby extending the cancer phenotype from mild to severe. Recent studies show that p53 isoforms are differentially expressed in different human tissues, and the loss-of-function or gain-of-function mutations within the isoforms can cause tissue-specific cancer or provide cancer stem cell potential in different tissues.{{cite journal | vauthors = Khoury MP, Bourdon JC | title = p53 Isoforms: An Intracellular Microprocessor? | journal = Genes & Cancer | volume = 2 | issue = 4 | pages = 453–65 | date = April 2011 | pmid = 21779513 | pmc = 3135639 | doi = 10.1177/1947601911408893 }}{{cite journal | vauthors = Avery-Kiejda KA, Morten B, Wong-Brown MW, Mathe A, Scott RJ | title = The relative mRNA expression of p53 isoforms in breast cancer is associated with clinical features and outcome | journal = Carcinogenesis | volume = 35 | issue = 3 | pages = 586–96 | date = March 2014 | pmid = 24336193 | doi = 10.1093/carcin/bgt411 | doi-access = free }}{{cite journal | vauthors = Arsic N, Gadea G, Lagerqvist EL, Busson M, Cahuzac N, Brock C, Hollande F, Gire V, Pannequin J, Roux P | title = The p53 isoform Δ133p53β promotes cancer stem cell potential | journal = Stem Cell Reports | volume = 4 | issue = 4 | pages = 531–40 | date = April 2015 | pmid = 25754205 | pmc = 4400643 | doi = 10.1016/j.stemcr.2015.02.001 }} TP53 mutation also hits energy metabolism and increases glycolysis in breast cancer cells.{{cite journal | vauthors = Harami-Papp H, Pongor LS, Munkácsy G, Horváth G, Nagy ÁM, Ambrus A, Hauser P, Szabó A, Tretter L, Győrffy B | title = TP53 mutation hits energy metabolism and increases glycolysis in breast cancer | journal = Oncotarget | volume = 7 | issue = 41 | pages = 67183–67195 | date = October 2016 | pmid = 27582538 | pmc = 5341867 | doi = 10.18632/oncotarget.11594 }}

The dynamics of p53 proteins, along with its antagonist Mdm2, indicate that the levels of p53, in units of concentration, oscillate as a function of time. This "damped" oscillation is both clinically documented {{cite journal | vauthors = Geva-Zatorsky N, Rosenfeld N, Itzkovitz S, Milo R, Sigal A, Dekel E, Yarnitzky T, Liron Y, Polak P, Lahav G, Alon U | title = Oscillations and variability in the p53 system | journal = Molecular Systems Biology | volume = 2 | pages = 2006.0033 | date = June 2006 | pmid = 16773083 | pmc = 1681500 | doi = 10.1038/msb4100068 }} and mathematically modelled.{{cite journal | vauthors = Proctor CJ, Gray DA | title = Explaining oscillations and variability in the p53-Mdm2 system | journal = BMC Systems Biology | volume = 2 | issue = 75 | pages = 75 | date = August 2008 | pmid = 18706112 | pmc = 2553322 | doi = 10.1186/1752-0509-2-75 | doi-access = free }}{{cite journal | vauthors = Chong KH, Samarasinghe S, Kulasiri D | title = Mathematical modelling of p53 basal dynamics and DNA damage response | journal = C-fACS | issue = 20th International Congress on Mathematical Modelling and Simulation | pages = 670–6 | date = December 2013| volume = 259 | doi = 10.1016/j.mbs.2014.10.010 | pmid = 25433195 }} Mathematical models also indicate that the p53 concentration oscillates much faster once teratogens, such as double-stranded breaks (DSB) or UV radiation, are introduced to the system. This supports and models the current understanding of p53 dynamics, where DNA damage induces p53 activation (see p53 regulation for more information). Current models can also be useful for modelling the mutations in p53 isoforms and their effects on p53 oscillation, thereby promoting de novo tissue-specific pharmacological drug discovery.{{cn|date=November 2024}}

p53 was identified in 1979 by Lionel Crawford, David P. Lane, Arnold Levine, and Lloyd Old, working at Imperial Cancer Research Fund (UK) Princeton University/UMDNJ (Cancer Institute of New Jersey), and Memorial Sloan Kettering Cancer Center, respectively. It had been hypothesized to exist before as the target of the SV40 virus, a strain that induced development of tumors. The name p53 is in fact a misnomer, as it describes the apparent molecular mass measured when it was first discovered, though it was later realised this was an overestimate: the correct molecular mass is only 43.7 kDa.{{cite journal | vauthors = Levine AJ, Oren M | title = The first 30 years of p53: growing ever more complex | journal = Nature Reviews. Cancer | volume = 9 | issue = 10 | pages = 749–758 | date = October 2009 | pmid = 19776744 | pmc = 2771725 | doi = 10.1038/nrc2723 }}

The TP53 gene from the mouse was first cloned by Peter Chumakov of The Academy of Sciences of the USSR in 1982,{{cite journal | vauthors = Chumakov PM, Iotsova VS, Georgiev GP | title = [Isolation of a plasmid clone containing the mRNA sequence for mouse nonviral T-antigen] | language = ru | journal = Doklady Akademii Nauk SSSR | volume = 267 | issue = 5 | pages = 1272–5 | year = 1982 | pmid = 6295732 }} and independently in 1983 by Moshe Oren in collaboration with David Givol (Weizmann Institute of Science).{{cite journal | vauthors = Oren M, Levine AJ | title = Molecular cloning of a cDNA specific for the murine p53 cellular tumor antigen | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 80 | issue = 1 | pages = 56–9 | date = January 1983 | pmid = 6296874 | pmc = 393308 | doi = 10.1073/pnas.80.1.56 | bibcode = 1983PNAS...80...56O | doi-access = free }}{{cite journal | vauthors = Zakut-Houri R, Oren M, Bienz B, Lavie V, Hazum S, Givol D | title = A single gene and a pseudogene for the cellular tumour antigen p53 | journal = Nature | volume = 306 | issue = 5943 | pages = 594–7 | year = 1983 | pmid = 6646235 | doi = 10.1038/306594a0 | bibcode = 1983Natur.306..594Z | s2cid = 4325094 }} The human TP53 gene was cloned in 1984 and the full length clone in 1985.{{cite journal | vauthors = Zakut-Houri R, Bienz-Tadmor B, Givol D, Oren M | title = Human p53 cellular tumor antigen: cDNA sequence and expression in COS cells | journal = The EMBO Journal | volume = 4 | issue = 5 | pages = 1251–5 | date = May 1985 | pmid = 4006916 | pmc = 554332 | doi = 10.1002/j.1460-2075.1985.tb03768.x}}

It was initially presumed to be an oncogene due to the use of mutated cDNA following purification of tumor cell mRNA. Its role as a tumor suppressor gene was revealed in 1989 by Bert Vogelstein at the Johns Hopkins School of Medicine and Arnold Levine at Princeton University.{{cite journal | vauthors = Baker SJ, Fearon ER, Nigro JM, Hamilton SR, Preisinger AC, Jessup JM, vanTuinen P, Ledbetter DH, Barker DF, Nakamura Y, White R, Vogelstein B | title = Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas | journal = Science | volume = 244 | issue = 4901 | pages = 217–21 | date = April 1989 | pmid = 2649981 | doi = 10.1126/science.2649981 | bibcode = 1989Sci...244..217B }}{{cite journal | vauthors = Finlay CA, Hinds PW, Levine AJ | title = The p53 proto-oncogene can act as a suppressor of transformation | journal = Cell | volume = 57 | issue = 7 | pages = 1083–93 | date = June 1989 | pmid = 2525423 | doi = 10.1016/0092-8674(89)90045-7 | doi-access = free }} p53 went on to be identified as a transcription factor by Guillermina Lozano working at MD Anderson Cancer Center.{{cite journal | vauthors = Raycroft L, Wu HY, Lozano G | title = Transcriptional activation by wild-type but not transforming mutants of the p53 anti-oncogene | journal = Science | volume = 249 | issue = 4972 | pages = 1049–1051 | date = August 1990 | pmid = 2144364 | doi = 10.1126/science.2144364 | pmc = 2935288 | bibcode = 1990Sci...249.1049R }}

Warren Maltzman, of the Waksman Institute of Rutgers University first demonstrated that TP53 was responsive to DNA damage in the form of ultraviolet radiation.{{cite journal | vauthors = Maltzman W, Czyzyk L | title = UV irradiation stimulates levels of p53 cellular tumor antigen in nontransformed mouse cells | journal = Molecular and Cellular Biology | volume = 4 | issue = 9 | pages = 1689–94 | date = September 1984 | pmid = 6092932 | pmc = 368974 | doi = 10.1128/mcb.4.9.1689 }} In a series of publications in 1991–92, Michael Kastan of Johns Hopkins University, reported that TP53 was a critical part of a signal transduction pathway that helped cells respond to DNA damage.{{cite journal | vauthors = Kastan MB, Kuerbitz SJ | title = Control of G1 arrest after DNA damage | journal = Environmental Health Perspectives | volume = 101 | issue = Suppl 5 | pages = 55–8 | date = December 1993 | pmid = 8013425 | pmc = 1519427 | doi = 10.2307/3431842 | jstor = 3431842 }}

In 1993, p53 was voted molecule of the year by Science magazine.{{cite journal | vauthors = Koshland DE | title = Molecule of the year | journal = Science | volume = 262 | issue = 5142 | pages = 1953 | date = December 1993 | pmid = 8266084 | doi = 10.1126/science.8266084 | doi-access = | bibcode = 1993Sci...262.1953K }}

As with 95% of human genes, TP53 encodes more than one protein. All these p53 proteins are called the p53 isoforms. These proteins range in size from 3.5 to 43.7 kDa. Several isoforms were discovered in 2005, and so far 12 human p53 isoforms have been identified (p53α, p53β, p53γ, ∆40p53α, ∆40p53β, ∆40p53γ, ∆133p53α, ∆133p53β, ∆133p53γ, ∆160p53α, ∆160p53β, ∆160p53γ). Furthermore, p53 isoforms are expressed in a tissue dependent manner and p53α is never expressed alone.{{cite journal | vauthors = Bourdon JC, Fernandes K, Murray-Zmijewski F, Liu G, Diot A, Xirodimas DP, Saville MK, Lane DP | title = p53 isoforms can regulate p53 transcriptional activity | journal = Genes & Development | volume = 19 | issue = 18 | pages = 2122–37 | date = September 2005 | pmid = 16131611 | pmc = 1221884 | doi = 10.1101/gad.1339905 }}

The full length p53 isoform proteins can be subdivided into different protein domains. Starting from the N-terminus, there are first the amino-terminal transcription-activation domains (TAD 1, TAD 2), which are needed to induce a subset of p53 target genes. This domain is followed by the proline rich domain (PXXP), whereby the motif PXXP is repeated (P is a proline and X can be any amino acid). It is required among others for p53 mediated apoptosis.{{cite journal | vauthors = Zhu J, Zhang S, Jiang J, Chen X | title = Definition of the p53 functional domains necessary for inducing apoptosis | journal = The Journal of Biological Chemistry | volume = 275 | issue = 51 | pages = 39927–34 | date = December 2000 | pmid = 10982799 | doi = 10.1074/jbc.M005676200 | doi-access = free }} Some isoforms lack the proline rich domain, such as Δ133p53β,γ and Δ160p53α,β,γ; hence some isoforms of p53 are not mediating apoptosis, emphasizing the diversifying roles of the TP53 gene. Afterwards there is the DNA binding domain (DBD), which enables the proteins to sequence specific binding. The C-terminus domain completes the protein. It includes the nuclear localization signal (NLS), the nuclear export signal (NES) and the oligomerisation domain (OD). The NLS and NES are responsible for the subcellular regulation of p53. Through the OD, p53 can form a tetramer and then bind to DNA. Among the isoforms, some domains can be missing, but all of them share most of the highly conserved DNA-binding domain. {{cn|date=November 2024}}

The isoforms are formed by different mechanisms. The beta and the gamma isoforms are generated by multiple splicing of intron 9, which leads to a different C-terminus. Furthermore, the usage of an internal promoter in intron 4 causes the ∆133 and ∆160 isoforms, which lack the TAD domain and a part of the DBD. Moreover, alternative initiation of translation at codon 40 or 160 bear the ∆40p53 and ∆160p53 isoforms.

Due to the isoformic nature of p53 proteins, there have been several sources of evidence showing that mutations within the TP53 gene giving rise to mutated isoforms are causative agents of various cancer phenotypes, from mild to severe, due to single mutation in the TP53 gene (refer to section Experimental analysis of p53 mutations for more details).

p53 has been shown to interact with:

{{div col|colwidth=20em}}

• AIMP2,{{cite journal | vauthors = Han JM, Park BJ, Park SG, Oh YS, Choi SJ, Lee SW, Hwang SK, Chang SH, Cho MH, Kim S | title = AIMP2/p38, the scaffold for the multi-tRNA synthetase complex, responds to genotoxic stresses via p53 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 32 | pages = 11206–11 | date = August 2008 | pmid = 18695251 | pmc = 2516205 | doi = 10.1073/pnas.0800297105 | bibcode = 2008PNAS..10511206H | doi-access = free }}
• ANKRD2,
• APTX,
• ATM,{{cite journal | vauthors = Fabbro M, Savage K, Hobson K, Deans AJ, Powell SN, McArthur GA, Khanna KK | title = BRCA1-BARD1 complexes are required for p53Ser-15 phosphorylation and a G1/S arrest following ionizing radiation-induced DNA damage | journal = The Journal of Biological Chemistry | volume = 279 | issue = 30 | pages = 31251–8 | date = July 2004 | pmid = 15159397 | doi = 10.1074/jbc.M405372200 | doi-access = free }}{{cite journal | vauthors = Kang J, Ferguson D, Song H, Bassing C, Eckersdorff M, Alt FW, Xu Y | title = Functional interaction of H2AX, NBS1, and p53 in ATM-dependent DNA damage responses and tumor suppression | journal = Molecular and Cellular Biology | volume = 25 | issue = 2 | pages = 661–70 | date = January 2005 | pmid = 15632067 | pmc = 543410 | doi = 10.1128/MCB.25.2.661-670.2005 }}{{cite journal | vauthors = Khanna KK, Keating KE, Kozlov S, Scott S, Gatei M, Hobson K, Taya Y, Gabrielli B, Chan D, Lees-Miller SP, Lavin MF | title = ATM associates with and phosphorylates p53: mapping the region of interaction | journal = Nature Genetics | volume = 20 | issue = 4 | pages = 398–400 | date = December 1998 | pmid = 9843217 | doi = 10.1038/3882 | s2cid = 23994762 }}{{cite journal | vauthors = Westphal CH, Schmaltz C, Rowan S, Elson A, Fisher DE, Leder P | title = Genetic interactions between atm and p53 influence cellular proliferation and irradiation-induced cell cycle checkpoints | journal = Cancer Research | volume = 57 | issue = 9 | pages = 1664–7 | date = May 1997 | pmid = 9135004 }}
• ATR,{{cite journal | vauthors = Kim ST, Lim DS, Canman CE, Kastan MB | title = Substrate specificities and identification of putative substrates of ATM kinase family members | journal = The Journal of Biological Chemistry | volume = 274 | issue = 53 | pages = 37538–43 | date = December 1999 | pmid = 10608806 | doi = 10.1074/jbc.274.53.37538 | doi-access = free }}
• ATF3,{{cite journal | vauthors = Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE | title = A human protein-protein interaction network: a resource for annotating the proteome | journal = Cell | volume = 122 | issue = 6 | pages = 957–68 | date = September 2005 | pmid = 16169070 | doi = 10.1016/j.cell.2005.08.029 | doi-access = free | hdl = 11858/00-001M-0000-0010-8592-0 | hdl-access = free }}{{cite journal | vauthors = Yan C, Wang H, Boyd DD | title = ATF3 represses 72-kDa type IV collagenase (MMP-2) expression by antagonizing p53-dependent trans-activation of the collagenase promoter | journal = The Journal of Biological Chemistry | volume = 277 | issue = 13 | pages = 10804–12 | date = March 2002 | pmid = 11792711 | doi = 10.1074/jbc.M112069200 | doi-access = free }}
• AURKA,{{cite journal | vauthors = Chen SS, Chang PC, Cheng YW, Tang FM, Lin YS | title = Suppression of the STK15 oncogenic activity requires a transactivation-independent p53 function | journal = The EMBO Journal | volume = 21 | issue = 17 | pages = 4491–9 | date = September 2002 | pmid = 12198151 | pmc = 126178 | doi = 10.1093/emboj/cdf409 }}
• BAK1,{{cite journal | vauthors = Leu JI, Dumont P, Hafey M, Murphy ME, George DL | title = Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex | journal = Nature Cell Biology | volume = 6 | issue = 5 | pages = 443–50 | date = May 2004 | pmid = 15077116 | doi = 10.1038/ncb1123 | s2cid = 43063712 }}
• BARD1,
• BLM,{{cite journal | vauthors = Wang XW, Tseng A, Ellis NA, Spillare EA, Linke SP, Robles AI, Seker H, Yang Q, Hu P, Beresten S, Bemmels NA, Garfield S, Harris CC | title = Functional interaction of p53 and BLM DNA helicase in apoptosis | journal = The Journal of Biological Chemistry | volume = 276 | issue = 35 | pages = 32948–55 | date = August 2001 | pmid = 11399766 | doi = 10.1074/jbc.M103298200 | doi-access = free }}{{cite journal | vauthors = Garkavtsev IV, Kley N, Grigorian IA, Gudkov AV | title = The Bloom syndrome protein interacts and cooperates with p53 in regulation of transcription and cell growth control | journal = Oncogene | volume = 20 | issue = 57 | pages = 8276–80 | date = December 2001 | pmid = 11781842 | doi = 10.1038/sj.onc.1205120 | s2cid = 13084911 | doi-access = }}
• BRCA1,{{cite journal | vauthors = Abramovitch S, Werner H | title = Functional and physical interactions between BRCA1 and p53 in transcriptional regulation of the IGF-IR gene | journal = Hormone and Metabolic Research | volume = 35 | issue = 11–12 | pages = 758–62 | year = 2003 | pmid = 14710355 | doi = 10.1055/s-2004-814154 | s2cid = 20898175 }}{{cite journal | vauthors = Ouchi T, Monteiro AN, August A, Aaronson SA, Hanafusa H | title = BRCA1 regulates p53-dependent gene expression | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 5 | pages = 2302–6 | date = March 1998 | pmid = 9482880 | pmc = 19327 | doi = 10.1073/pnas.95.5.2302 | bibcode = 1998PNAS...95.2302O | doi-access = free }}{{cite journal | vauthors = Chai YL, Cui J, Shao N, Shyam E, Reddy P, Rao VN | title = The second BRCT domain of BRCA1 proteins interacts with p53 and stimulates transcription from the p21WAF1/CIP1 promoter | journal = Oncogene | volume = 18 | issue = 1 | pages = 263–8 | date = January 1999 | pmid = 9926942 | doi = 10.1038/sj.onc.1202323 | s2cid = 7462625 | doi-access = }}{{cite journal | vauthors = Zhang H, Somasundaram K, Peng Y, Tian H, Zhang H, Bi D, Weber BL, El-Deiry WS | title = BRCA1 physically associates with p53 and stimulates its transcriptional activity | journal = Oncogene | volume = 16 | issue = 13 | pages = 1713–21 | date = April 1998 | pmid = 9582019 | doi = 10.1038/sj.onc.1201932 | s2cid = 24616900 | doi-access = }}
• BRCA2,{{cite journal | vauthors = Marmorstein LY, Ouchi T, Aaronson SA | title = The BRCA2 gene product functionally interacts with p53 and RAD51 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 23 | pages = 13869–74 | date = November 1998 | pmid = 9811893 | pmc = 24938 | doi = 10.1073/pnas.95.23.13869 | bibcode = 1998PNAS...9513869M | doi-access = free }}
• BRCC3,
• BRE,{{cite journal | vauthors = Dong Y, Hakimi MA, Chen X, Kumaraswamy E, Cooch NS, Godwin AK, Shiekhattar R | title = Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair | journal = Molecular Cell | volume = 12 | issue = 5 | pages = 1087–99 | date = November 2003 | pmid = 14636569 | doi = 10.1016/S1097-2765(03)00424-6 | doi-access = free }}
• CEBPZ,{{cite journal | vauthors = Uramoto H, Izumi H, Nagatani G, Ohmori H, Nagasue N, Ise T, Yoshida T, Yasumoto K, Kohno K | title = Physical interaction of tumour suppressor p53/p73 with CCAAT-binding transcription factor 2 (CTF2) and differential regulation of human high-mobility group 1 (HMG1) gene expression | journal = The Biochemical Journal | volume = 371 | issue = Pt 2 | pages = 301–10 | date = April 2003 | pmid = 12534345 | pmc = 1223307 | doi = 10.1042/BJ20021646 }}
• CDC14A,
• Cdk1,{{cite journal | vauthors = Luciani MG, Hutchins JR, Zheleva D, Hupp TR | title = The C-terminal regulatory domain of p53 contains a functional docking site for cyclin A | journal = Journal of Molecular Biology | volume = 300 | issue = 3 | pages = 503–18 | date = July 2000 | pmid = 10884347 | doi = 10.1006/jmbi.2000.3830 }}{{cite journal | vauthors = Ababneh M, Götz C, Montenarh M | title = Downregulation of the cdc2/cyclin B protein kinase activity by binding of p53 to p34(cdc2) | journal = Biochemical and Biophysical Research Communications | volume = 283 | issue = 2 | pages = 507–12 | date = May 2001 | pmid = 11327730 | doi = 10.1006/bbrc.2001.4792 }}
• CFLAR,{{cite journal | vauthors = Abedini MR, Muller EJ, Brun J, Bergeron R, Gray DA, Tsang BK | title = Cisplatin induces p53-dependent FLICE-like inhibitory protein ubiquitination in ovarian cancer cells | journal = Cancer Research | volume = 68 | issue = 12 | pages = 4511–7 | date = June 2008 | pmid = 18559494 | doi = 10.1158/0008-5472.CAN-08-0673 | doi-access = free }}
• CHEK1,{{cite journal | vauthors = Sengupta S, Robles AI, Linke SP, Sinogeeva NI, Zhang R, Pedeux R, Ward IM, Celeste A, Nussenzweig A, Chen J, Halazonetis TD, Harris CC | title = Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest | journal = The Journal of Cell Biology | volume = 166 | issue = 6 | pages = 801–13 | date = September 2004 | pmid = 15364958 | pmc = 2172115 | doi = 10.1083/jcb.200405128 }}{{cite journal | vauthors = Tian H, Faje AT, Lee SL, Jorgensen TJ | title = Radiation-induced phosphorylation of Chk1 at S345 is associated with p53-dependent cell cycle arrest pathways | journal = Neoplasia | volume = 4 | issue = 2 | pages = 171–80 | year = 2002 | pmid = 11896572 | pmc = 1550321 | doi = 10.1038/sj.neo.7900219 }}
• CCNG1,{{cite journal | vauthors = Zhao L, Samuels T, Winckler S, Korgaonkar C, Tompkins V, Horne MC, Quelle DE | title = Cyclin G1 has growth inhibitory activity linked to the ARF-Mdm2-p53 and pRb tumor suppressor pathways | journal = Molecular Cancer Research | volume = 1 | issue = 3 | pages = 195–206 | date = January 2003 | pmid = 12556559 }}
• CREBBP,{{cite journal | vauthors = Ito A, Kawaguchi Y, Lai CH, Kovacs JJ, Higashimoto Y, Appella E, Yao TP | title = MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation | journal = The EMBO Journal | volume = 21 | issue = 22 | pages = 6236–45 | date = November 2002 | pmid = 12426395 | pmc = 137207 | doi = 10.1093/emboj/cdf616 }}
• CREB1,{{cite journal | vauthors = Giebler HA, Lemasson I, Nyborg JK | title = p53 recruitment of CREB binding protein mediated through phosphorylated CREB: a novel pathway of tumor suppressor regulation | journal = Molecular and Cellular Biology | volume = 20 | issue = 13 | pages = 4849–58 | date = July 2000 | pmid = 10848610 | pmc = 85936 | doi = 10.1128/MCB.20.13.4849-4858.2000 }}
• Cyclin H,{{cite journal | vauthors = Schneider E, Montenarh M, Wagner P | title = Regulation of CAK kinase activity by p53 | journal = Oncogene | volume = 17 | issue = 21 | pages = 2733–41 | date = November 1998 | pmid = 9840937 | doi = 10.1038/sj.onc.1202504 | s2cid = 6281777 | doi-access = }}
• CDK7,{{cite journal | vauthors = Ko LJ, Shieh SY, Chen X, Jayaraman L, Tamai K, Taya Y, Prives C, Pan ZQ | title = p53 is phosphorylated by CDK7-cyclin H in a p36MAT1-dependent manner | journal = Molecular and Cellular Biology | volume = 17 | issue = 12 | pages = 7220–9 | date = December 1997 | pmid = 9372954 | pmc = 232579 | doi = 10.1128/mcb.17.12.7220 }}
• DNA-PKcs,{{cite journal | vauthors = Goudelock DM, Jiang K, Pereira E, Russell B, Sanchez Y | title = Regulatory interactions between the checkpoint kinase Chk1 and the proteins of the DNA-dependent protein kinase complex | journal = The Journal of Biological Chemistry | volume = 278 | issue = 32 | pages = 29940–7 | date = August 2003 | pmid = 12756247 | doi = 10.1074/jbc.M301765200 | doi-access = free }}{{cite journal | vauthors = Yavuzer U, Smith GC, Bliss T, Werner D, Jackson SP | title = DNA end-independent activation of DNA-PK mediated via association with the DNA-binding protein C1D | journal = Genes & Development | volume = 12 | issue = 14 | pages = 2188–99 | date = July 1998 | pmid = 9679063 | pmc = 317006 | doi = 10.1101/gad.12.14.2188 }}
• E4F1,{{cite journal | vauthors = Rizos H, Diefenbach E, Badhwar P, Woodruff S, Becker TM, Rooney RJ, Kefford RF | title = Association of p14ARF with the p120E4F transcriptional repressor enhances cell cycle inhibition | journal = The Journal of Biological Chemistry | volume = 278 | issue = 7 | pages = 4981–9 | date = February 2003 | pmid = 12446718 | doi = 10.1074/jbc.M210978200 | doi-access = free }}{{cite journal | vauthors = Sandy P, Gostissa M, Fogal V, Cecco LD, Szalay K, Rooney RJ, Schneider C, Del Sal G | title = p53 is involved in the p120E4F-mediated growth arrest | journal = Oncogene | volume = 19 | issue = 2 | pages = 188–99 | date = January 2000 | pmid = 10644996 | doi = 10.1038/sj.onc.1203250 | doi-access = free }}
• EFEMP2,{{cite journal | vauthors = Gallagher WM, Argentini M, Sierra V, Bracco L, Debussche L, Conseiller E | title = MBP1: a novel mutant p53-specific protein partner with oncogenic properties | journal = Oncogene | volume = 18 | issue = 24 | pages = 3608–16 | date = June 1999 | pmid = 10380882 | doi = 10.1038/sj.onc.1202937 | doi-access = free }}
• EIF2AK2,{{cite journal | vauthors = Cuddihy AR, Wong AH, Tam NW, Li S, Koromilas AE | title = The double-stranded RNA activated protein kinase PKR physically associates with the tumor suppressor p53 protein and phosphorylates human p53 on serine 392 in vitro | journal = Oncogene | volume = 18 | issue = 17 | pages = 2690–702 | date = April 1999 | pmid = 10348343 | doi = 10.1038/sj.onc.1202620 | s2cid = 22467088 | doi-access = }}
• ELL,{{cite journal | vauthors = Shinobu N, Maeda T, Aso T, Ito T, Kondo T, Koike K, Hatakeyama M | title = Physical interaction and functional antagonism between the RNA polymerase II elongation factor ELL and p53 | journal = The Journal of Biological Chemistry | volume = 274 | issue = 24 | pages = 17003–10 | date = June 1999 | pmid = 10358050 | doi = 10.1074/jbc.274.24.17003 | doi-access = free }}
• EP300,{{cite journal | vauthors = Livengood JA, Scoggin KE, Van Orden K, McBryant SJ, Edayathumangalam RS, Laybourn PJ, Nyborg JK | title = p53 Transcriptional activity is mediated through the SRC1-interacting domain of CBP/p300 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 11 | pages = 9054–61 | date = March 2002 | pmid = 11782467 | doi = 10.1074/jbc.M108870200 | doi-access = free }}{{cite journal | vauthors = Grossman SR, Perez M, Kung AL, Joseph M, Mansur C, Xiao ZX, Kumar S, Howley PM, Livingston DM | title = p300/MDM2 complexes participate in MDM2-mediated p53 degradation | journal = Molecular Cell | volume = 2 | issue = 4 | pages = 405–15 | date = October 1998 | pmid = 9809062 | doi = 10.1016/S1097-2765(00)80140-9 | doi-access = free }}{{cite journal | vauthors = An W, Kim J, Roeder RG | title = Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53 | journal = Cell | volume = 117 | issue = 6 | pages = 735–48 | date = June 2004 | pmid = 15186775 | doi = 10.1016/j.cell.2004.05.009 | doi-access = free }}{{cite journal | vauthors = Pastorcic M, Das HK | title = Regulation of transcription of the human presenilin-1 gene by ets transcription factors and the p53 protooncogene | journal = The Journal of Biological Chemistry | volume = 275 | issue = 45 | pages = 34938–45 | date = November 2000 | pmid = 10942770 | doi = 10.1074/jbc.M005411200 | doi-access = free }}
• ERCC6,{{cite journal | vauthors = Wang XW, Yeh H, Schaeffer L, Roy R, Moncollin V, Egly JM, Wang Z, Freidberg EC, Evans MK, Taffe BG | title = p53 modulation of TFIIH-associated nucleotide excision repair activity | journal = Nature Genetics | volume = 10 | issue = 2 | pages = 188–95 | date = June 1995 | pmid = 7663514 | doi = 10.1038/ng0695-188 | hdl = 1765/54884 | s2cid = 38325851 | url = http://repub.eur.nl/pub/54884 | hdl-access = free }}{{cite journal | vauthors = Yu A, Fan HY, Liao D, Bailey AD, Weiner AM | title = Activation of p53 or loss of the Cockayne syndrome group B repair protein causes metaphase fragility of human U1, U2, and 5S genes | journal = Molecular Cell | volume = 5 | issue = 5 | pages = 801–10 | date = May 2000 | pmid = 10882116 | doi = 10.1016/S1097-2765(00)80320-2 | doi-access = free }}
• GNL3,{{cite journal | vauthors = Tsai RY, McKay RD | title = A nucleolar mechanism controlling cell proliferation in stem cells and cancer cells | journal = Genes & Development | volume = 16 | issue = 23 | pages = 2991–3003 | date = December 2002 | pmid = 12464630 | pmc = 187487 | doi = 10.1101/gad.55671 }}
• GPS2,{{cite journal | vauthors = Peng YC, Kuo F, Breiding DE, Wang YF, Mansur CP, Androphy EJ | title = AMF1 (GPS2) modulates p53 transactivation | journal = Molecular and Cellular Biology | volume = 21 | issue = 17 | pages = 5913–24 | date = September 2001 | pmid = 11486030 | pmc = 87310 | doi = 10.1128/MCB.21.17.5913-5924.2001 }}
• GSK3B,{{cite journal | vauthors = Watcharasit P, Bijur GN, Zmijewski JW, Song L, Zmijewska A, Chen X, Johnson GV, Jope RS | title = Direct, activating interaction between glycogen synthase kinase-3beta and p53 after DNA damage | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 12 | pages = 7951–5 | date = June 2002 | pmid = 12048243 | pmc = 123001 | doi = 10.1073/pnas.122062299 | bibcode = 2002PNAS...99.7951W | doi-access = free }}
• HSP90AA1,{{cite journal | vauthors = Wang C, Chen J | title = Phosphorylation and hsp90 binding mediate heat shock stabilization of p53 | journal = The Journal of Biological Chemistry | volume = 278 | issue = 3 | pages = 2066–71 | date = January 2003 | pmid = 12427754 | doi = 10.1074/jbc.M206697200 | doi-access = free }}{{cite journal | vauthors = Peng Y, Chen L, Li C, Lu W, Chen J | title = Inhibition of MDM2 by hsp90 contributes to mutant p53 stabilization | journal = The Journal of Biological Chemistry | volume = 276 | issue = 44 | pages = 40583–90 | date = November 2001 | pmid = 11507088 | doi = 10.1074/jbc.M102817200 | doi-access = free }}
• HIF1A,{{cite journal | vauthors = Chen D, Li M, Luo J, Gu W | title = Direct interactions between HIF-1 alpha and Mdm2 modulate p53 function | journal = The Journal of Biological Chemistry | volume = 278 | issue = 16 | pages = 13595–8 | date = April 2003 | pmid = 12606552 | doi = 10.1074/jbc.C200694200 | doi-access = free }}{{cite journal | vauthors = Ravi R, Mookerjee B, Bhujwalla ZM, Sutter CH, Artemov D, Zeng Q, Dillehay LE, Madan A, Semenza GL, Bedi A | title = Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha | journal = Genes & Development | volume = 14 | issue = 1 | pages = 34–44 | date = January 2000 | pmid = 10640274 | pmc = 316350 | doi = 10.1101/gad.14.1.34 }}{{cite journal | vauthors = Hansson LO, Friedler A, Freund S, Rudiger S, Fersht AR | title = Two sequence motifs from HIF-1alpha bind to the DNA-binding site of p53 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 16 | pages = 10305–9 | date = August 2002 | pmid = 12124396 | pmc = 124909 | doi = 10.1073/pnas.122347199 | bibcode = 2002PNAS...9910305H | doi-access = free }}{{cite journal | vauthors = An WG, Kanekal M, Simon MC, Maltepe E, Blagosklonny MV, Neckers LM | title = Stabilization of wild-type p53 by hypoxia-inducible factor 1alpha | journal = Nature | volume = 392 | issue = 6674 | pages = 405–8 | date = March 1998 | pmid = 9537326 | doi = 10.1038/32925 | bibcode = 1998Natur.392..405A | s2cid = 4423081 }}
• HIPK1,{{cite journal | vauthors = Kondo S, Lu Y, Debbas M, Lin AW, Sarosi I, Itie A, Wakeham A, Tuan J, Saris C, Elliott G, Ma W, Benchimol S, Lowe SW, Mak TW, Thukral SK | title = Characterization of cells and gene-targeted mice deficient for the p53-binding kinase homeodomain-interacting protein kinase 1 (HIPK1) | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 9 | pages = 5431–6 | date = April 2003 | pmid = 12702766 | pmc = 154362 | doi = 10.1073/pnas.0530308100 | bibcode = 2003PNAS..100.5431K | doi-access = free }}
• HIPK2,{{cite journal | vauthors = Hofmann TG, Möller A, Sirma H, Zentgraf H, Taya Y, Dröge W, Will H, Schmitz ML | title = Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2 | journal = Nature Cell Biology | volume = 4 | issue = 1 | pages = 1–10 | date = January 2002 | pmid = 11740489 | doi = 10.1038/ncb715 | s2cid = 37789883 }}{{cite journal | vauthors = Kim EJ, Park JS, Um SJ | title = Identification and characterization of HIPK2 interacting with p73 and modulating functions of the p53 family in vivo | journal = The Journal of Biological Chemistry | volume = 277 | issue = 35 | pages = 32020–8 | date = August 2002 | pmid = 11925430 | doi = 10.1074/jbc.M200153200 | doi-access = free}}
• HMGB1,{{cite journal | vauthors = Imamura T, Izumi H, Nagatani G, Ise T, Nomoto M, Iwamoto Y, Kohno K | title = Interaction with p53 enhances binding of cisplatin-modified DNA by high mobility group 1 protein | journal = The Journal of Biological Chemistry | volume = 276 | issue = 10 | pages = 7534–40 | date = March 2001 | pmid = 11106654 | doi = 10.1074/jbc.M008143200 | doi-access = free }}{{cite journal | vauthors = Dintilhac A, Bernués J | title = HMGB1 interacts with many apparently unrelated proteins by recognizing short amino acid sequences | journal = The Journal of Biological Chemistry | volume = 277 | issue = 9 | pages = 7021–8 | date = March 2002 | pmid = 11748221 | doi = 10.1074/jbc.M108417200 | doi-access = free | hdl = 10261/112516 | hdl-access = free }}
• HSPA9,{{cite journal | vauthors = Wadhwa R, Yaguchi T, Hasan MK, Mitsui Y, Reddel RR, Kaul SC | title = Hsp70 family member, mot-2/mthsp70/GRP75, binds to the cytoplasmic sequestration domain of the p53 protein | journal = Experimental Cell Research | volume = 274 | issue = 2 | pages = 246–53 | date = April 2002 | pmid = 11900485 | doi = 10.1006/excr.2002.5468 }}
• Huntingtin,{{cite journal | vauthors = Steffan JS, Kazantsev A, Spasic-Boskovic O, Greenwald M, Zhu YZ, Gohler H, Wanker EE, Bates GP, Housman DE, Thompson LM | title = The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 12 | pages = 6763–8 | date = June 2000 | pmid = 10823891 | pmc = 18731 | doi = 10.1073/pnas.100110097 | bibcode = 2000PNAS...97.6763S | doi-access = free }}
• ING1,{{cite journal | vauthors = Leung KM, Po LS, Tsang FC, Siu WY, Lau A, Ho HT, Poon RY | title = The candidate tumor suppressor ING1b can stabilize p53 by disrupting the regulation of p53 by MDM2 | journal = Cancer Research | volume = 62 | issue = 17 | pages = 4890–3 | date = September 2002 | pmid = 12208736 }}{{cite journal | vauthors = Garkavtsev I, Grigorian IA, Ossovskaya VS, Chernov MV, Chumakov PM, Gudkov AV | title = The candidate tumour suppressor p33ING1 cooperates with p53 in cell growth control | journal = Nature | volume = 391 | issue = 6664 | pages = 295–8 | date = January 1998 | pmid = 9440695 | doi = 10.1038/34675 | bibcode = 1998Natur.391..295G | s2cid = 4429461 }}
• ING4,{{cite journal | vauthors = Tsai KW, Tseng HC, Lin WC | title = Two wobble-splicing events affect ING4 protein subnuclear localization and degradation | journal = Experimental Cell Research | volume = 314 | issue = 17 | pages = 3130–41 | date = October 2008 | pmid = 18775696 | doi = 10.1016/j.yexcr.2008.08.002 }}
• ING5,{{cite journal | vauthors = Shiseki M, Nagashima M, Pedeux RM, Kitahama-Shiseki M, Miura K, Okamura S, Onogi H, Higashimoto Y, Appella E, Yokota J, Harris CC | title = p29ING4 and p28ING5 bind to p53 and p300, and enhance p53 activity | journal = Cancer Research | volume = 63 | issue = 10 | pages = 2373–8 | date = May 2003 | pmid = 12750254 }}
• IκBα,{{cite journal | vauthors = Chang NS | title = The non-ankyrin C terminus of Ikappa Balpha physically interacts with p53 in vivo and dissociates in response to apoptotic stress, hypoxia, DNA damage, and transforming growth factor-beta 1-mediated growth suppression | journal = The Journal of Biological Chemistry | volume = 277 | issue = 12 | pages = 10323–31 | date = March 2002 | pmid = 11799106 | doi = 10.1074/jbc.M106607200 | doi-access = free }}
• KPNB1,{{cite journal | vauthors = Akakura S, Yoshida M, Yoneda Y, Horinouchi S | title = A role for Hsc70 in regulating nucleocytoplasmic transport of a temperature-sensitive p53 (p53Val-135) | journal = The Journal of Biological Chemistry | volume = 276 | issue = 18 | pages = 14649–57 | date = May 2001 | pmid = 11297531 | doi = 10.1074/jbc.M100200200 | doi-access = free }}
• LMO3,
• Mdm2,
• MDM4,{{cite journal | vauthors = Badciong JC, Haas AL | title = MdmX is a RING finger ubiquitin ligase capable of synergistically enhancing Mdm2 ubiquitination | journal = The Journal of Biological Chemistry | volume = 277 | issue = 51 | pages = 49668–75 | date = December 2002 | pmid = 12393902 | doi = 10.1074/jbc.M208593200 | doi-access = free }}{{cite journal | vauthors = Shvarts A, Bazuine M, Dekker P, Ramos YF, Steegenga WT, Merckx G, van Ham RC, van der Houven van Oordt W, van der Eb AJ, Jochemsen AG | title = Isolation and identification of the human homolog of a new p53-binding protein, Mdmx | journal = Genomics | volume = 43 | issue = 1 | pages = 34–42 | date = July 1997 | pmid = 9226370 | doi = 10.1006/geno.1997.4775 | hdl = 2066/142231 | s2cid = 11794685 | url = https://repository.ubn.ru.nl/bitstream/2066/142231/1/142231.pdf | hdl-access = free }}
• MED1,{{cite journal | vauthors = Frade R, Balbo M, Barel M | title = RB18A, whose gene is localized on chromosome 17q12-q21.1, regulates in vivo p53 transactivating activity | journal = Cancer Research | volume = 60 | issue = 23 | pages = 6585–9 | date = December 2000 | pmid = 11118038 }}{{cite journal | vauthors = Drané P, Barel M, Balbo M, Frade R | title = Identification of RB18A, a 205 kDa new p53 regulatory protein which shares antigenic and functional properties with p53 | journal = Oncogene | volume = 15 | issue = 25 | pages = 3013–24 | date = December 1997 | pmid = 9444950 | doi = 10.1038/sj.onc.1201492 | doi-access = free }}
• MAPK9,{{cite journal | vauthors = Hu MC, Qiu WR, Wang YP | title = JNK1, JNK2 and JNK3 are p53 N-terminal serine 34 kinases | journal = Oncogene | volume = 15 | issue = 19 | pages = 2277–87 | date = November 1997 | pmid = 9393873 | doi = 10.1038/sj.onc.1201401 | doi-access = free }}{{cite journal | vauthors = Lin Y, Khokhlatchev A, Figeys D, Avruch J | title = Death-associated protein 4 binds MST1 and augments MST1-induced apoptosis | journal = The Journal of Biological Chemistry | volume = 277 | issue = 50 | pages = 47991–8001 | date = December 2002 | pmid = 12384512 | doi = 10.1074/jbc.M202630200 | doi-access = free }}
• MNAT1,
• NDN,{{cite journal | vauthors = Taniura H, Matsumoto K, Yoshikawa K | title = Physical and functional interactions of neuronal growth suppressor necdin with p53 | journal = The Journal of Biological Chemistry | volume = 274 | issue = 23 | pages = 16242–8 | date = June 1999 | pmid = 10347180 | doi = 10.1074/jbc.274.23.16242 | doi-access = free }}
• NCL,{{cite journal | vauthors = Daniely Y, Dimitrova DD, Borowiec JA | title = Stress-dependent nucleolin mobilization mediated by p53-nucleolin complex formation | journal = Molecular and Cellular Biology | volume = 22 | issue = 16 | pages = 6014–22 | date = August 2002 | pmid = 12138209 | pmc = 133981 | doi = 10.1128/MCB.22.16.6014-6022.2002 }}
• NUMB,{{cite journal | vauthors = Colaluca IN, Tosoni D, Nuciforo P, Senic-Matuglia F, Galimberti V, Viale G, Pece S, Di Fiore PP | title = NUMB controls p53 tumour suppressor activity | journal = Nature | volume = 451 | issue = 7174 | pages = 76–80 | date = January 2008 | pmid = 18172499 | doi = 10.1038/nature06412 | bibcode = 2008Natur.451...76C | s2cid = 4431258 }}
• NF-κB,
• P16,{{cite journal | vauthors = Zhang Y, Xiong Y, Yarbrough WG | title = ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways | journal = Cell | volume = 92 | issue = 6 | pages = 725–34 | date = March 1998 | pmid = 9529249 | doi = 10.1016/S0092-8674(00)81401-4 | doi-access = free }}
• PARC,{{cite journal | vauthors = Nikolaev AY, Li M, Puskas N, Qin J, Gu W | title = Parc: a cytoplasmic anchor for p53 | journal = Cell | volume = 112 | issue = 1 | pages = 29–40 | date = January 2003 | pmid = 12526791 | doi = 10.1016/S0092-8674(02)01255-2 | doi-access = free }}
• PARP1,{{cite journal | vauthors = Gueven N, Becherel OJ, Kijas AW, Chen P, Howe O, Rudolph JH, Gatti R, Date H, Onodera O, Taucher-Scholz G, Lavin MF | title = Aprataxin, a novel protein that protects against genotoxic stress | journal = Human Molecular Genetics | volume = 13 | issue = 10 | pages = 1081–93 | date = May 2004 | pmid = 15044383 | doi = 10.1093/hmg/ddh122 | doi-access = free }}{{cite journal | vauthors = Malanga M, Pleschke JM, Kleczkowska HE, Althaus FR | title = Poly(ADP-ribose) binds to specific domains of p53 and alters its DNA binding functions | journal = The Journal of Biological Chemistry | volume = 273 | issue = 19 | pages = 11839–43 | date = May 1998 | pmid = 9565608 | doi = 10.1074/jbc.273.19.11839 | doi-access = free }}
• PIAS1,{{cite journal | vauthors = Kahyo T, Nishida T, Yasuda H | title = Involvement of PIAS1 in the sumoylation of tumor suppressor p53 | journal = Molecular Cell | volume = 8 | issue = 3 | pages = 713–8 | date = September 2001 | pmid = 11583632 | doi = 10.1016/S1097-2765(01)00349-5 | doi-access = free }}
• CDC14B,{{cite journal | vauthors = Li L, Ljungman M, Dixon JE | title = The human Cdc14 phosphatases interact with and dephosphorylate the tumor suppressor protein p53 | journal = The Journal of Biological Chemistry | volume = 275 | issue = 4 | pages = 2410–4 | date = January 2000 | pmid = 10644693 | doi = 10.1074/jbc.275.4.2410 | doi-access = free }}
• PIN1,{{cite journal | vauthors = Wulf GM, Liou YC, Ryo A, Lee SW, Lu KP | title = Role of Pin1 in the regulation of p53 stability and p21 transactivation, and cell cycle checkpoints in response to DNA damage | journal = The Journal of Biological Chemistry | volume = 277 | issue = 50 | pages = 47976–9 | date = December 2002 | pmid = 12388558 | doi = 10.1074/jbc.C200538200 | doi-access = free }}{{cite journal | vauthors = Zacchi P, Gostissa M, Uchida T, Salvagno C, Avolio F, Volinia S, Ronai Z, Blandino G, Schneider C, Del Sal G | title = The prolyl isomerase Pin1 reveals a mechanism to control p53 functions after genotoxic insults | journal = Nature | volume = 419 | issue = 6909 | pages = 853–7 | date = October 2002 | pmid = 12397362 | doi = 10.1038/nature01120 | bibcode = 2002Natur.419..853Z | s2cid = 4311658 }}
• PLAGL1,{{cite journal | vauthors = Huang SM, Schönthal AH, Stallcup MR | title = Enhancement of p53-dependent gene activation by the transcriptional coactivator Zac1 | journal = Oncogene | volume = 20 | issue = 17 | pages = 2134–43 | date = April 2001 | pmid = 11360197 | doi = 10.1038/sj.onc.1204298 | s2cid = 21331603 | doi-access = }}
• PLK3,{{cite journal | vauthors = Xie S, Wu H, Wang Q, Cogswell JP, Husain I, Conn C, Stambrook P, Jhanwar-Uniyal M, Dai W | title = Plk3 functionally links DNA damage to cell cycle arrest and apoptosis at least in part via the p53 pathway | journal = The Journal of Biological Chemistry | volume = 276 | issue = 46 | pages = 43305–12 | date = November 2001 | pmid = 11551930 | doi = 10.1074/jbc.M106050200 | doi-access = free }}{{cite journal | vauthors = Bahassi EM, Conn CW, Myer DL, Hennigan RF, McGowan CH, Sanchez Y, Stambrook PJ | title = Mammalian Polo-like kinase 3 (Plk3) is a multifunctional protein involved in stress response pathways | journal = Oncogene | volume = 21 | issue = 43 | pages = 6633–40 | date = September 2002 | pmid = 12242661 | doi = 10.1038/sj.onc.1205850 | s2cid = 24106070 | doi-access = }}
• PRKRA,{{cite journal | vauthors = Simons A, Melamed-Bessudo C, Wolkowicz R, Sperling J, Sperling R, Eisenbach L, Rotter V | title = PACT: cloning and characterization of a cellular p53 binding protein that interacts with Rb | journal = Oncogene | volume = 14 | issue = 2 | pages = 145–55 | date = January 1997 | pmid = 9010216 | doi = 10.1038/sj.onc.1200825 | doi-access = free }}
• PHB,{{cite journal | vauthors = Fusaro G, Dasgupta P, Rastogi S, Joshi B, Chellappan S | title = Prohibitin induces the transcriptional activity of p53 and is exported from the nucleus upon apoptotic signaling | journal = The Journal of Biological Chemistry | volume = 278 | issue = 48 | pages = 47853–61 | date = November 2003 | pmid = 14500729 | doi = 10.1074/jbc.M305171200 | doi-access = free }}
• PML,{{cite journal | vauthors = Kurki S, Latonen L, Laiho M | title = Cellular stress and DNA damage invoke temporally distinct Mdm2, p53 and PML complexes and damage-specific nuclear relocalization | journal = Journal of Cell Science | volume = 116 | issue = Pt 19 | pages = 3917–25 | date = October 2003 | pmid = 12915590 | doi = 10.1242/jcs.00714 | doi-access = free }}{{cite journal | vauthors = Fogal V, Gostissa M, Sandy P, Zacchi P, Sternsdorf T, Jensen K, Pandolfi PP, Will H, Schneider C, Del Sal G | title = Regulation of p53 activity in nuclear bodies by a specific PML isoform | journal = The EMBO Journal | volume = 19 | issue = 22 | pages = 6185–95 | date = November 2000 | pmid = 11080164 | pmc = 305840 | doi = 10.1093/emboj/19.22.6185 }}{{cite journal | vauthors = Guo A, Salomoni P, Luo J, Shih A, Zhong S, Gu W, Pandolfi PP | title = The function of PML in p53-dependent apoptosis | journal = Nature Cell Biology | volume = 2 | issue = 10 | pages = 730–6 | date = October 2000 | pmid = 11025664 | doi = 10.1038/35036365 | s2cid = 13480833 }}
• PSME3,{{cite journal | vauthors = Zhang Z, Zhang R | title = Proteasome activator PA28 gamma regulates p53 by enhancing its MDM2-mediated degradation | journal = The EMBO Journal | volume = 27 | issue = 6 | pages = 852–64 | date = March 2008 | pmid = 18309296 | pmc = 2265109 | doi = 10.1038/emboj.2008.25 }}
• PTEN,{{cite journal | vauthors = Freeman DJ, Li AG, Wei G, Li HH, Kertesz N, Lesche R, Whale AD, Martinez-Diaz H, Rozengurt N, Cardiff RD, Liu X, Wu H | title = PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent mechanisms | journal = Cancer Cell | volume = 3 | issue = 2 | pages = 117–30 | date = February 2003 | pmid = 12620407 | doi = 10.1016/S1535-6108(03)00021-7 | doi-access = free }}
• PTK2,{{cite journal | vauthors = Lim ST, Chen XL, Lim Y, Hanson DA, Vo TT, Howerton K, Larocque N, Fisher SJ, Schlaepfer DD, Ilic D | title = Nuclear FAK promotes cell proliferation and survival through FERM-enhanced p53 degradation | journal = Molecular Cell | volume = 29 | issue = 1 | pages = 9–22 | date = January 2008 | pmid = 18206965 | pmc = 2234035 | doi = 10.1016/j.molcel.2007.11.031 }}
• PTTG1,{{cite journal | vauthors = Bernal JA, Luna R, Espina A, Lázaro I, Ramos-Morales F, Romero F, Arias C, Silva A, Tortolero M, Pintor-Toro JA | title = Human securin interacts with p53 and modulates p53-mediated transcriptional activity and apoptosis | journal = Nature Genetics | volume = 32 | issue = 2 | pages = 306–11 | date = October 2002 | pmid = 12355087 | doi = 10.1038/ng997 | s2cid = 1770399 }}
• RAD51,{{cite journal | vauthors = Stürzbecher HW, Donzelmann B, Henning W, Knippschild U, Buchhop S | title = p53 is linked directly to homologous recombination processes via RAD51/RecA protein interaction | journal = The EMBO Journal | volume = 15 | issue = 8 | pages = 1992–2002 | date = April 1996 | pmid = 8617246 | pmc = 450118 | doi = 10.1002/j.1460-2075.1996.tb00550.x}}{{cite journal | vauthors = Buchhop S, Gibson MK, Wang XW, Wagner P, Stürzbecher HW, Harris CC | title = Interaction of p53 with the human Rad51 protein | journal = Nucleic Acids Research | volume = 25 | issue = 19 | pages = 3868–74 | date = October 1997 | pmid = 9380510 | pmc = 146972 | doi = 10.1093/nar/25.19.3868 }}
• RCHY1,{{cite journal | vauthors = Leng RP, Lin Y, Ma W, Wu H, Lemmers B, Chung S, Parant JM, Lozano G, Hakem R, Benchimol S | title = Pirh2, a p53-induced ubiquitin-protein ligase, promotes p53 degradation | journal = Cell | volume = 112 | issue = 6 | pages = 779–91 | date = March 2003 | pmid = 12654245 | doi = 10.1016/S0092-8674(03)00193-4 | doi-access = free }}{{cite journal | vauthors = Sheng Y, Laister RC, Lemak A, Wu B, Tai E, Duan S, Lukin J, Sunnerhagen M, Srisailam S, Karra M, Benchimol S, Arrowsmith CH | title = Molecular basis of Pirh2-mediated p53 ubiquitylation | journal = Nature Structural & Molecular Biology | volume = 15 | issue = 12 | pages = 1334–42 | date = December 2008 | pmid = 19043414 | pmc = 4075976 | doi = 10.1038/nsmb.1521 }}
• RELA,
• Reprimo{{citation needed|date=March 2021}}
• RPA1,{{cite journal | vauthors = Romanova LY, Willers H, Blagosklonny MV, Powell SN | title = The interaction of p53 with replication protein A mediates suppression of homologous recombination | journal = Oncogene | volume = 23 | issue = 56 | pages = 9025–33 | date = December 2004 | pmid = 15489903 | doi = 10.1038/sj.onc.1207982 | s2cid = 23482723 | doi-access = }}{{cite journal | vauthors = Riva F, Zuco V, Vink AA, Supino R, Prosperi E | title = UV-induced DNA incision and proliferating cell nuclear antigen recruitment to repair sites occur independently of p53-replication protein A interaction in p53 wild type and mutant ovarian carcinoma cells | journal = Carcinogenesis | volume = 22 | issue = 12 | pages = 1971–8 | date = December 2001 | pmid = 11751427 | doi = 10.1093/carcin/22.12.1971 | doi-access = }}
• RPL11,{{cite journal | vauthors = Zhang Y, Wolf GW, Bhat K, Jin A, Allio T, Burkhart WA, Xiong Y | title = Ribosomal protein L11 negatively regulates oncoprotein MDM2 and mediates a p53-dependent ribosomal-stress checkpoint pathway | journal = Molecular and Cellular Biology | volume = 23 | issue = 23 | pages = 8902–12 | date = December 2003 | pmid = 14612427 | pmc = 262682 | doi = 10.1128/MCB.23.23.8902-8912.2003 }}
• S100B,{{cite journal | vauthors = Lin J, Yang Q, Yan Z, Markowitz J, Wilder PT, Carrier F, Weber DJ | title = Inhibiting S100B restores p53 levels in primary malignant melanoma cancer cells | journal = The Journal of Biological Chemistry | volume = 279 | issue = 32 | pages = 34071–7 | date = August 2004 | pmid = 15178678 | doi = 10.1074/jbc.M405419200 | doi-access = free }}
• SUMO1,{{cite journal | vauthors = Minty A, Dumont X, Kaghad M, Caput D | title = Covalent modification of p73alpha by SUMO-1. Two-hybrid screening with p73 identifies novel SUMO-1-interacting proteins and a SUMO-1 interaction motif | journal = The Journal of Biological Chemistry | volume = 275 | issue = 46 | pages = 36316–23 | date = November 2000 | pmid = 10961991 | doi = 10.1074/jbc.M004293200 | doi-access = free }}{{cite journal | vauthors = Ivanchuk SM, Mondal S, Rutka JT | title = p14ARF interacts with DAXX: effects on HDM2 and p53 | journal = Cell Cycle | volume = 7 | issue = 12 | pages = 1836–50 | date = June 2008 | pmid = 18583933 | doi = 10.4161/cc.7.12.6025 | doi-access = free }}
• SMARCA4,
• SMARCB1,{{cite journal | vauthors = Lee D, Kim JW, Seo T, Hwang SG, Choi EJ, Choe J | title = SWI/SNF complex interacts with tumor suppressor p53 and is necessary for the activation of p53-mediated transcription | journal = The Journal of Biological Chemistry | volume = 277 | issue = 25 | pages = 22330–7 | date = June 2002 | pmid = 11950834 | doi = 10.1074/jbc.M111987200 | doi-access = free}}
• SMN1,{{cite journal | vauthors = Young PJ, Day PM, Zhou J, Androphy EJ, Morris GE, Lorson CL | title = A direct interaction between the survival motor neuron protein and p53 and its relationship to spinal muscular atrophy | journal = The Journal of Biological Chemistry | volume = 277 | issue = 4 | pages = 2852–9 | date = January 2002 | pmid = 11704667 | doi = 10.1074/jbc.M108769200 | doi-access = free }}
• STAT3,{{cite journal | vauthors = Choy MK, Movassagh M, Siggens L, Vujic A, Goddard M, Sánchez A, Perkins N, Figg N, Bennett M, Carroll J, Foo R | title = High-throughput sequencing identifies STAT3 as the DNA-associated factor for p53-NF-kappaB-complex-dependent gene expression in human heart failure | journal = Genome Medicine | volume = 2 | issue = 6 | pages = 37 | date = June 2010 | pmid = 20546595 | pmc = 2905097 | doi = 10.1186/gm158 | doi-access = free }}
• TBP,{{cite journal | vauthors = Seto E, Usheva A, Zambetti GP, Momand J, Horikoshi N, Weinmann R, Levine AJ, Shenk T | title = Wild-type p53 binds to the TATA-binding protein and represses transcription | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 24 | pages = 12028–32 | date = December 1992 | pmid = 1465435 | pmc = 50691 | doi = 10.1073/pnas.89.24.12028 | bibcode = 1992PNAS...8912028S | doi-access = free }}{{cite journal | vauthors = Cvekl A, Kashanchi F, Brady JN, Piatigorsky J | title = Pax-6 interactions with TATA-box-binding protein and retinoblastoma protein | journal = Investigative Ophthalmology & Visual Science | volume = 40 | issue = 7 | pages = 1343–50 | date = June 1999 | pmid = 10359315 }}
• TFAP2A,{{cite journal | vauthors = McPherson LA, Loktev AV, Weigel RJ | title = Tumor suppressor activity of AP2alpha mediated through a direct interaction with p53 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 47 | pages = 45028–33 | date = November 2002 | pmid = 12226108 | doi = 10.1074/jbc.M208924200 | doi-access = free }}
• TFDP1,{{cite journal | vauthors = Sørensen TS, Girling R, Lee CW, Gannon J, Bandara LR, La Thangue NB | title = Functional interaction between DP-1 and p53 | journal = Molecular and Cellular Biology | volume = 16 | issue = 10 | pages = 5888–95 | date = October 1996 | pmid = 8816502 | pmc = 231590 | doi = 10.1128/mcb.16.10.5888 }}
• TIGAR,{{cite journal | vauthors = Green DR, Chipuk JE | title = p53 and metabolism: Inside the TIGAR | journal = Cell | volume = 126 | issue = 1 | pages = 30–2 | date = July 2006 | pmid = 16839873 | doi = 10.1016/j.cell.2006.06.032 | doi-access = free }}
• TOP1,{{cite journal | vauthors = Gobert C, Skladanowski A, Larsen AK | title = The interaction between p53 and DNA topoisomerase I is regulated differently in cells with wild-type and mutant p53 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 18 | pages = 10355–60 | date = August 1999 | pmid = 10468612 | pmc = 17892 | doi = 10.1073/pnas.96.18.10355 | bibcode = 1999PNAS...9610355G | doi-access = free }}{{cite journal | vauthors = Mao Y, Mehl IR, Muller MT | title = Subnuclear distribution of topoisomerase I is linked to ongoing transcription and p53 status | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 3 | pages = 1235–40 | date = February 2002 | pmid = 11805286 | pmc = 122173 | doi = 10.1073/pnas.022631899 | bibcode = 2002PNAS...99.1235M | doi-access = free }}
• TOP2A,
• TP53BP1,{{cite journal | vauthors = Derbyshire DJ, Basu BP, Serpell LC, Joo WS, Date T, Iwabuchi K, Doherty AJ | title = Crystal structure of human 53BP1 BRCT domains bound to p53 tumour suppressor | journal = The EMBO Journal | volume = 21 | issue = 14 | pages = 3863–72 | date = July 2002 | pmid = 12110597 | pmc = 126127 | doi = 10.1093/emboj/cdf383 }}{{cite journal | vauthors = Ekblad CM, Friedler A, Veprintsev D, Weinberg RL, Itzhaki LS | title = Comparison of BRCT domains of BRCA1 and 53BP1: a biophysical analysis | journal = Protein Science | volume = 13 | issue = 3 | pages = 617–25 | date = March 2004 | pmid = 14978302 | pmc = 2286730 | doi = 10.1110/ps.03461404 }}{{cite journal | vauthors = Lo KW, Kan HM, Chan LN, Xu WG, Wang KP, Wu Z, Sheng M, Zhang M | title = The 8-kDa dynein light chain binds to p53-binding protein 1 and mediates DNA damage-induced p53 nuclear accumulation | journal = The Journal of Biological Chemistry | volume = 280 | issue = 9 | pages = 8172–9 | date = March 2005 | pmid = 15611139 | doi = 10.1074/jbc.M411408200 | doi-access = free }}{{cite journal | vauthors = Joo WS, Jeffrey PD, Cantor SB, Finnin MS, Livingston DM, Pavletich NP | title = Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure | journal = Genes & Development | volume = 16 | issue = 5 | pages = 583–93 | date = March 2002 | pmid = 11877378 | pmc = 155350 | doi = 10.1101/gad.959202 }}{{cite journal | vauthors = Derbyshire DJ, Basu BP, Date T, Iwabuchi K, Doherty AJ | title = Purification, crystallization and preliminary X-ray analysis of the BRCT domains of human 53BP1 bound to the p53 tumour suppressor | journal = Acta Crystallographica D | volume = 58 | issue = Pt 10 Pt 2 | pages = 1826–9 | date = October 2002 | pmid = 12351827 | doi = 10.1107/S0907444902010910 | bibcode = 2002AcCrD..58.1826D }}
• TP53BP2,{{cite journal | vauthors = Iwabuchi K, Bartel PL, Li B, Marraccino R, Fields S | title = Two cellular proteins that bind to wild-type but not mutant p53 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 91 | issue = 13 | pages = 6098–102 | date = June 1994 | pmid = 8016121 | pmc = 44145 | doi = 10.1073/pnas.91.13.6098 | bibcode = 1994PNAS...91.6098I | doi-access = free }}{{cite journal | vauthors = Naumovski L, Cleary ML | title = The p53-binding protein 53BP2 also interacts with Bc12 and impedes cell cycle progression at G2/M | journal = Molecular and Cellular Biology | volume = 16 | issue = 7 | pages = 3884–92 | date = July 1996 | pmid = 8668206 | pmc = 231385 | doi = 10.1128/MCB.16.7.3884}}
• TOP2B,{{cite journal | vauthors = Cowell IG, Okorokov AL, Cutts SA, Padget K, Bell M, Milner J, Austin CA | title = Human topoisomerase IIalpha and IIbeta interact with the C-terminal region of p53 | journal = Experimental Cell Research | volume = 255 | issue = 1 | pages = 86–94 | date = February 2000 | pmid = 10666337 | doi = 10.1006/excr.1999.4772 }}
• TP53INP1,{{cite journal | vauthors = Tomasini R, Samir AA, Carrier A, Isnardon D, Cecchinelli B, Soddu S, Malissen B, Dagorn JC, Iovanna JL, Dusetti NJ | title = TP53INP1s and homeodomain-interacting protein kinase-2 (HIPK2) are partners in regulating p53 activity | journal = The Journal of Biological Chemistry | volume = 278 | issue = 39 | pages = 37722–9 | date = September 2003 | pmid = 12851404 | doi = 10.1074/jbc.M301979200 | doi-access = free }}{{cite journal | vauthors = Okamura S, Arakawa H, Tanaka T, Nakanishi H, Ng CC, Taya Y, Monden M, Nakamura Y | title = p53DINP1, a p53-inducible gene, regulates p53-dependent apoptosis | journal = Molecular Cell | volume = 8 | issue = 1 | pages = 85–94 | date = July 2001 | pmid = 11511362 | doi = 10.1016/S1097-2765(01)00284-2 | doi-access = free }}
• TSG101,{{cite journal | vauthors = Li L, Liao J, Ruland J, Mak TW, Cohen SN | title = A TSG101/MDM2 regulatory loop modulates MDM2 degradation and MDM2/p53 feedback control | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 4 | pages = 1619–24 | date = February 2001 | pmid = 11172000 | pmc = 29306 | doi = 10.1073/pnas.98.4.1619 | bibcode = 2001PNAS...98.1619L | doi-access = free }}
• UBE2A,{{cite journal | vauthors = Lyakhovich A, Shekhar MP | title = Supramolecular complex formation between Rad6 and proteins of the p53 pathway during DNA damage-induced response | journal = Molecular and Cellular Biology | volume = 23 | issue = 7 | pages = 2463–75 | date = April 2003 | pmid = 12640129 | pmc = 150718 | doi = 10.1128/MCB.23.7.2463-2475.2003 }}
• UBE2I,{{cite journal | vauthors = Shen Z, Pardington-Purtymun PE, Comeaux JC, Moyzis RK, Chen DJ | title = Associations of UBE2I with RAD52, UBL1, p53, and RAD51 proteins in a yeast two-hybrid system | journal = Genomics | volume = 37 | issue = 2 | pages = 183–6 | date = October 1996 | pmid = 8921390 | doi = 10.1006/geno.1996.0540 | url = https://zenodo.org/record/1229705 }}{{cite journal | vauthors = Bernier-Villamor V, Sampson DA, Matunis MJ, Lima CD | title = Structural basis for E2-mediated SUMO conjugation revealed by a complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1 | journal = Cell | volume = 108 | issue = 3 | pages = 345–56 | date = February 2002 | pmid = 11853669 | doi = 10.1016/S0092-8674(02)00630-X | doi-access = free }}
• UBC,{{cite journal | vauthors = Sehat B, Andersson S, Girnita L, Larsson O | title = Identification of c-Cbl as a new ligase for insulin-like growth factor-I receptor with distinct roles from Mdm2 in receptor ubiquitination and endocytosis | journal = Cancer Research | volume = 68 | issue = 14 | pages = 5669–77 | date = July 2008 | pmid = 18632619 | doi = 10.1158/0008-5472.CAN-07-6364 | doi-access = }}{{cite journal | vauthors = Song MS, Song SJ, Kim SY, Oh HJ, Lim DS | title = The tumour suppressor RASSF1A promotes MDM2 self-ubiquitination by disrupting the MDM2-DAXX-HAUSP complex | journal = The EMBO Journal | volume = 27 | issue = 13 | pages = 1863–74 | date = July 2008 | pmid = 18566590 | pmc = 2486425 | doi = 10.1038/emboj.2008.115 }}{{cite journal | vauthors = Yang W, Dicker DT, Chen J, El-Deiry WS | title = CARPs enhance p53 turnover by degrading 14-3-3sigma and stabilizing MDM2 | journal = Cell Cycle | volume = 7 | issue = 5 | pages = 670–82 | date = March 2008 | pmid = 18382127 | doi = 10.4161/cc.7.5.5701 | doi-access = free }}{{cite journal | vauthors = Abe Y, Oda-Sato E, Tobiume K, Kawauchi K, Taya Y, Okamoto K, Oren M, Tanaka N | title = Hedgehog signaling overrides p53-mediated tumor suppression by activating Mdm2 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 12 | pages = 4838–43 | date = March 2008 | pmid = 18359851 | pmc = 2290789 | doi = 10.1073/pnas.0712216105 | bibcode = 2008PNAS..105.4838A | doi-access = free }}{{cite journal | vauthors = Dohmesen C, Koeppel M, Dobbelstein M | title = Specific inhibition of Mdm2-mediated neddylation by Tip60 | journal = Cell Cycle | volume = 7 | issue = 2 | pages = 222–31 | date = January 2008 | pmid = 18264029 | doi = 10.4161/cc.7.2.5185 | s2cid = 8023403 | doi-access = }}
• USP7,{{cite journal | vauthors = Li M, Chen D, Shiloh A, Luo J, Nikolaev AY, Qin J, Gu W | title = Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization | journal = Nature | volume = 416 | issue = 6881 | pages = 648–53 | date = April 2002 | pmid = 11923872 | doi = 10.1038/nature737 | bibcode = 2002Natur.416..648L | s2cid = 4389394 }}
• USP10,{{cite journal | vauthors = Yuan J, Luo K, Zhang L, Cheville JC, Lou Z| title = USP10 Regulates p53 Localization and Stability by Deubiquitinating p53 | journal = Cell | volume = 140 | issue = 3 | pages = 384–396 | date = February 2010 | pmid = 20096447 | doi = 10.1016/j.cell.2009.12.032 | pmc = 2820153 | doi-access = free }}
• WRN,{{cite journal | vauthors = Yang Q, Zhang R, Wang XW, Spillare EA, Linke SP, Subramanian D, Griffith JD, Li JL, Hickson ID, Shen JC, Loeb LA, Mazur SJ, Appella E, Brosh RM, Karmakar P, Bohr VA, Harris CC | title = The processing of Holliday junctions by BLM and WRN helicases is regulated by p53 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 35 | pages = 31980–7 | date = August 2002 | pmid = 12080066 | doi = 10.1074/jbc.M204111200 | doi-access = free | hdl = 10026.1/10341 | hdl-access = free }}{{cite journal | vauthors = Brosh RM, Karmakar P, Sommers JA, Yang Q, Wang XW, Spillare EA, Harris CC, Bohr VA | title = p53 Modulates the exonuclease activity of Werner syndrome protein | journal = The Journal of Biological Chemistry | volume = 276 | issue = 37 | pages = 35093–102 | date = September 2001 | pmid = 11427532 | doi = 10.1074/jbc.M103332200 | doi-access = free }}
• WWOX,{{cite journal | vauthors = Chang NS, Pratt N, Heath J, Schultz L, Sleve D, Carey GB, Zevotek N | title = Hyaluronidase induction of a WW domain-containing oxidoreductase that enhances tumor necrosis factor cytotoxicity | journal = The Journal of Biological Chemistry | volume = 276 | issue = 5 | pages = 3361–70 | date = February 2001 | pmid = 11058590 | doi = 10.1074/jbc.M007140200 | doi-access = free }}
• XPB,
• YBX1,{{cite journal | vauthors = Kojic S, Medeot E, Guccione E, Krmac H, Zara I, Martinelli V, Valle G, Faulkner G | title = The Ankrd2 protein, a link between the sarcomere and the nucleus in skeletal muscle | journal = Journal of Molecular Biology | volume = 339 | issue = 2 | pages = 313–25 | date = May 2004 | pmid = 15136035 | doi = 10.1016/j.jmb.2004.03.071 }}{{cite journal | vauthors = Okamoto T, Izumi H, Imamura T, Takano H, Ise T, Uchiumi T, Kuwano M, Kohno K | title = Direct interaction of p53 with the Y-box binding protein, YB-1: a mechanism for regulation of human gene expression | journal = Oncogene | volume = 19 | issue = 54 | pages = 6194–202 | date = December 2000 | pmid = 11175333 | doi = 10.1038/sj.onc.1204029 | s2cid = 19222684 | doi-access = }}
• YPEL3,{{cite journal | vauthors = Kelley KD, Miller KR, Todd A, Kelley AR, Tuttle R, Berberich SJ | title = YPEL3, a p53-regulated gene that induces cellular senescence | journal = Cancer Research | volume = 70 | issue = 9 | pages = 3566–75 | date = May 2010 | pmid = 20388804 | pmc = 2862112 | doi = 10.1158/0008-5472.CAN-09-3219 }}
• YWHAZ,{{cite journal | vauthors = Waterman MJ, Stavridi ES, Waterman JL, Halazonetis TD | title = ATM-dependent activation of p53 involves dephosphorylation and association with 14-3-3 proteins | journal = Nature Genetics | volume = 19 | issue = 2 | pages = 175–8 | date = June 1998 | pmid = 9620776 | doi = 10.1038/542 | s2cid = 26600934 }}
• Zif268,{{cite journal | vauthors = Liu J, Grogan L, Nau MM, Allegra CJ, Chu E, Wright JJ | title = Physical interaction between p53 and primary response gene Egr-1 | journal = International Journal of Oncology | volume = 18 | issue = 4 | pages = 863–70 | date = April 2001 | pmid = 11251186 | doi = 10.3892/ijo.18.4.863 }}
• ZNF148,{{cite journal | vauthors = Bai L, Merchant JL | title = ZBP-89 promotes growth arrest through stabilization of p53 | journal = Molecular and Cellular Biology | volume = 21 | issue = 14 | pages = 4670–83 | date = July 2001 | pmid = 11416144 | pmc = 87140 | doi = 10.1128/MCB.21.14.4670-4683.2001 }}
• SIRT1,{{cite journal | vauthors = Yamakuchi M, Lowenstein CJ | title = MiR-34, SIRT1 and p53: the feedback loop | journal = Cell Cycle | volume = 8 | issue = 5 | pages = 712–5 | date = March 2009 | pmid = 19221490 | doi = 10.4161/cc.8.5.7753 | doi-access = free }}
• circRNA_014511.{{cite journal | vauthors = Wang Y, Zhang J, Li J, Gui R, Nie X, Huang R | title = CircRNA_014511 affects the radiosensitivity of bone marrow mesenchymal stem cells by binding to miR-29b-2-5p | journal = Bosnian Journal of Basic Medical Sciences | volume = 19 | issue = 2 | pages = 155–163 | date = May 2019 | pmid = 30640591 | pmc = 6535393 | doi = 10.17305/bjbms.2019.3935 }}

{{div col end}}

• Eprenetapopt, a reactivator of some mutant forms of p53
• Pifithrin, an inhibitor of p53

{{reflist|group=note}}

{{reflist}}

{{Commons category|Tumor suppressor protein p53}}

• {{cite web|url=http://p53.bii.a-star.edu.sg/|title=p53 Knowledgebase|access-date=2008-04-06 | publisher=Lane Group at the Institute of Molecular and Cell Biology (IMCB), Singapore| archive-url=https://web.archive.org/web/20060103170051/http://p53.bii.a-star.edu.sg/| archive-date=2006-01-03|url-status=dead}}
• [https://www.ncbi.nlm.nih.gov/books/NBK1311/ GeneReviews/NCBI/NIH/UW entry on Li-Fraumeni Syndrome]
• [https://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 TUMOR PROTEIN p53] @ OMIM
• [http://www.news-medical.net/news/20130708/p53-restoration-of-function-drug-candidate-an-interview-with-Dr-Wayne-Danter-MD-FRCPC-President-and-CEO-of-Critical-Outcome-Technologies.aspx p53 restoration of function]
• [http://atlasgeneticsoncology.org/Genes/P53ID88.html p53] @ The Atlas of Genetics and Cytogenetics in Oncology and Haematology
• [https://www.genecards.org/cgi-bin/carddisp.pl?gene=tp53 TP53 Gene] @ GeneCards
• [https://web.archive.org/web/20101124135159/http://insciences.org/articles.php?tag=p53 p53 News] provided by insciences organisation
• {{cite web|url=http://pdb101.rcsb.org/motm/31|title= p53 Tumor Suppressor|access-date=2008-04-06| vauthors = Goodsel DS |date=2002-07-01| work=Molecule of the Month|publisher=RCSB Protein Data Bank}}
• {{cite web|url=http://p53.free.fr/|title=p53 Web Site|access-date=2008-04-06| vauthors = Soussi T }}
• [https://livinglfs.org/ Living LFS] A non-profit Li-Fraumeni Syndrome patient support organization
• [http://www.tp53.co.uk/ The George Pantziarka TP53 Trust] A support group from the UK for people with Li-Fraumeni Syndrome or other TP53-related disorders
• [http://www-p53.iarc.fr/ IARC TP53 Somatic Mutations database] maintained at IARC, Lyon, by Magali Olivier
• [https://www.ebi.ac.uk/pdbe/pdbe-kb/proteins/P04637 PDBe-KB] provides an overview of all the structure information available in the PDB for Human P53.
• [https://www.youtube.com/watch?v=gY1p-xdHbQg|title= scientific animation] conformational changes of p53 upon binding to DNA

{{PDB Gallery|geneid=7157}}

{{Transcription factors|g4}}

{{Tumor suppressor genes and oncogenes}}

{{Cell cycle proteins}}

Category:Programmed cell death

Category:Proteins

Category:Transcription factors

Category:Tumor suppressor genes

Category:Apoptosis

Category:Genes mutated in mice

Category:Aging-related proteins