AP-1 transcription factor

AP-1 was first discovered as a TPA-activated transcription factor that bound to a cis-regulatory element of the human metallothionein IIa (hMTIIa) promoter and SV40.{{cite journal | vauthors = Lee W, Haslinger A, Karin M, Tjian R | title = Activation of transcription by two factors that bind promoter and enhancer sequences of the human metallothionein gene and SV40 | journal = Nature | volume = 325 | issue = 6102 | pages = 368–72 | date = January 1987 | pmid = 3027570 | doi = 10.1038/325368a0 | bibcode = 1987Natur.325..368L | s2cid = 4314423 }} The AP-1 binding site was identified as the 12-O-Tetradecanoylphorbol-13-acetate (TPA) response element (TRE) with the consensus sequence 5’-TGA G/C TCA-3’.{{cite journal | vauthors = Angel P, Imagawa M, Chiu R, Stein B, Imbra RJ, Rahmsdorf HJ, Jonat C, Herrlich P, Karin M | title = Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor | journal = Cell | volume = 49 | issue = 6 | pages = 729–39 | date = June 1987 | pmid = 3034432 | doi = 10.1016/0092-8674(87)90611-8 | s2cid = 23154076 }} The AP-1 subunit Jun was identified as a novel oncoprotein of avian sarcoma virus, and Fos-associated p39 protein was identified as the transcript of the cellular Jun gene. Fos was first isolated as the cellular homologue of two viral v-fos oncogenes, both of which induce osteosarcoma in mice and rats.{{cite journal | vauthors = Wagner EF | title = AP-1--Introductory remarks | journal = Oncogene | volume = 20 | issue = 19 | pages = 2334–5 | date = April 2001 | pmid = 11402330 | doi = 10.1038/sj.onc.1204416 | doi-access = free }} Since its discovery, AP-1 has been found to be associated with numerous regulatory and physiological processes, and new relationships are still being investigated.

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| footer = C-JUN homodimer ({{PDB|1JUN}}) Left: The helical wheel projection of c-jun homodimer. When viewed down the axis, the alpha helices have a ~7 amino acid repeating leucine at position a. Two helices may be aligned so that repeating hydrophobic side chains (gray) form an interacting surface which facilitates dimerization. Dashed lines indicate potential electrostatic bridges. Right: Side view of c-jun homodimer. Residues on position a and d in helical wheel diagram are shown. Leucines are colored in blue, and other hydrophobic residues are colored in yellow.

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AP-1 transcription factor is assembled through the dimerization of a characteristic bZIP domain (basic region leucine zipper) in the Fos and Jun subunits. A typical bZIP domain consists of a “leucine zipper” region, and a “basic region”. The leucine zipper is responsible for dimerization of the Jun and Fos protein subunits. This structural motif twists two alpha helical protein domains into a “coiled coil,” characterized by a periodicity of 3.5 residues per turn and repetitive leucines appearing at every seventh position of the polypeptide chain. Due to the amino acid sequence and the periodicity of the helices, the leucine side chains are arranged along one face of the α helix and form a hydrophobic surface that modulates dimerization.{{cite journal | vauthors = Landschulz WH, Johnson PF, McKnight SL | title = The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins | journal = Science | volume = 240 | issue = 4860 | pages = 1759–64 | date = June 1988 | pmid = 3289117 | doi = 10.1126/science.3289117 | bibcode = 1988Sci...240.1759L }} Hydrophobic residues additional to leucine also form the characteristic 3-4 repeat of α helices involved in “coiled-coil” interactions, and help contribute to the hydrophobic packing that drives dimerization. Together, this hydrophobic surface holds the two subunits together.{{cite journal | vauthors = O'Shea EK, Rutkowski R, Kim PS | title = Evidence that the leucine zipper is a coiled coil | journal = Science | volume = 243 | issue = 4890 | pages = 538–42 | date = January 1989 | pmid = 2911757 | doi = 10.1126/science.2911757 | bibcode = 1989Sci...243..538O }}{{cite journal | vauthors = O'Shea EK, Rutkowski R, Stafford WF, Kim PS | title = Preferential heterodimer formation by isolated leucine zippers from fos and jun | journal = Science | volume = 245 | issue = 4918 | pages = 646–8 | date = August 1989 | pmid = 2503872 | doi = 10.1126/science.2503872 | bibcode = 1989Sci...245..646O }}

The basic region of the bZIP domain is just upstream to the leucine zipper, and contains positively charged residues. This region interacts with DNA target sites.{{cite journal | vauthors = Vogt PK, Bos TJ | title = jun: oncogene and transcription factor | journal = Advances in Cancer Research | volume = 55 | pages = 1–35 | date = 1990 | doi = 10.1016/s0065-230x(08)60466-2 | pmid = 2166997 | isbn = 9780120066551 }} Apart from the “leucine zipper” and the “basic region” which are important for dimerization and DNA-binding, the c-jun protein contains three short regions, which consist of clusters of negatively charged amino acids in its N-terminal half that are important for transcriptional activation in vivo.{{cite journal | vauthors = Angel P, Karin M | title = The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation | journal = Biochimica et Biophysica Acta (BBA) - Reviews on Cancer | volume = 1072 | issue = 2–3 | pages = 129–57 | date = December 1991 | pmid = 1751545 | doi = 10.1016/0304-419X(91)90011-9 }}

Dimerization happens between the products of the c-jun and c-fos protooncogenes, and is required for DNA-binding. Jun proteins can form both homo and heterodimers and therefore are capable of binding to DNA by themselves. However, Fos proteins do not dimerize with each other and therefore can only bind to DNA when bound with Jun.{{cite journal | vauthors = Kouzarides T, Ziff E | title = The role of the leucine zipper in the fos-jun interaction | journal = Nature | volume = 336 | issue = 6200 | pages = 646–51 | date = December 1988 | pmid = 2974122 | doi = 10.1038/336646a0 | bibcode = 1988Natur.336..646K | s2cid = 4355663 }}{{cite journal | vauthors = Nakabeppu Y, Ryder K, Nathans D | title = DNA binding activities of three murine Jun proteins: stimulation by Fos | journal = Cell | volume = 55 | issue = 5 | pages = 907–15 | date = December 1988 | pmid = 3142691 | doi = 10.1016/0092-8674(88)90146-8 | s2cid = 11057487 }} The Jun-Fos heterodimer is more stable and has higher DNA-binding activity than Jun homodimers.

AP-1 transcription factor has been shown to have a hand in a wide range of cellular processes, including cell growth, differentiation, and apoptosis. AP-1 activity is often regulated via post-translational modifications, DNA binding dimer composition, and interaction with various binding partners. AP-1 transcription factors are also associated with numerous physiological functions especially in determination of organisms’ life span and tissue regeneration. Below are some of the other important functions and biological roles AP-1 transcription factors have been shown to be involved in.

The AP-1 transcription factor has been shown to play numerous roles in cell growth and proliferation. In particular, c-Fos and c-Jun seem to be major players in these processes. C-jun has been shown to be essential for fibroblast proliferation,{{cite journal | vauthors = Karin M, Liu Z, Zandi E | title = AP-1 function and regulation | journal = Current Opinion in Cell Biology | volume = 9 | issue = 2 | pages = 240–6 | date = April 1997 | pmid = 9069263 | doi = 10.1016/S0955-0674(97)80068-3 }} and levels of both AP-1 subunits have been shown to be expressed above basal levels during cell division.{{cite journal| vauthors = Yamashita J, McCauley LK |title=The Activating Protein-1 Transcriptional Complex: Essential and Multifaceted Roles in Bone|journal=Clinical Reviews in Bone and Mineral Metabolism|date=2006|volume=4|issue=2|pages=107–122|doi=10.1385/BMM:4:2:107|s2cid=90318354}} C-fos has also been shown to increase in expression in response to the introduction of growth factors in the cell, further supporting its suggested involvement in the cell cycle. The growth factors TGF alpha, TGF beta, and IL2 have all been shown to stimulate c-Fos, and thereby stimulate cellular proliferation via AP-1 activation.

Cellular senescence has been identified as "a dynamic and reversible process regulated by (in)activation of a predetermined enhancer landscape controlled by the pioneer transcription factor AP-1", which "defines the organizational principles of the transcription factor network that drives the transcriptional programme of senescent cells".{{cite journal| vauthors = Zumerle S, Alimonti A |title= In and out from senescence|journal=Nat Cell Biol|date=2020|volume=22|issue=7|pages=753–754|doi=10.1038/s41556-020-0540-x|pmid= 32591745|s2cid= 220071911|doi-access=free}}{{cite journal| vauthors = Martínez-Zamudio R, Roux P, de Freitas J, et al |title= AP-1 imprints a reversible transcriptional programme of senescent cells|journal=Nat Cell Biol|date=2020|volume=22|issue=7|pages=842–855|doi=10.1038/s41556-020-0529-5|pmid= 32514071|s2cid= 219543898|pmc=7899185}}

AP-1 transcription is deeply involved in the modulation of gene expression. Changes in cellular gene expression in the initiation of DNA synthesis and the formation of differentiated derivatives can lead to cellular differentiation. AP-1 has been shown to be involved in cell differentiation in several systems. For example, by forming stable heterodimers with c-Jun, the bZIP region of c-Fos increases the binding of c-Jun to target genes whose activation is involved in the differentiation of chicken embryo fibroblasts (CEF).{{cite journal | vauthors = Shaulian E, Karin M | title = AP-1 as a regulator of cell life and death | journal = Nature Cell Biology | volume = 4 | issue = 5 | pages = E131–6 | date = May 2002 | pmid = 11988758 | doi = 10.1038/ncb0502-e131 | s2cid = 34337538 }} It has also been shown to participate in endoderm specification.{{cite journal | vauthors=Madrigal P, Deng S, Feng Y, Militi S, Goh KJ, Nibhani R, Grandy R, Osnato A, Ortmann D, Brown S, Pauklin S | title=Epigenetic and transcriptional regulations prime cell fate before division during human pluripotent stem cell differentiation | journal=Nature Communications | volume=14 | issue=405 | date=January 25, 2023 | page=405 | pmid=36697417 | doi =10.1038/s41467-023-36116-9 | pmc=9876972 | bibcode=2023NatCo..14..405M | url=https://www.nature.com/articles/s41467-023-36116-9.pdf }}

AP-1 transcription factor is associated with a broad range of apoptosis related interactions. AP-1 activity is induced by numerous extracellular matrix and genotoxic agents, suggesting involvement in programmed cell death. Many of these stimuli activate the c-Jun N-terminal kinases (JNKs) leading to the phosphorylation of Jun proteins and enhanced transcriptional activity of AP-1 dependent genes. Increases in the levels of Jun and Fos proteins and JNK activity have been reported in scenarios in which cells undergo apoptosis. For example, inactivated c-Jun-ER cells show a normal morphology, while c-Jun-ER activated cells have been shown to be apoptotic.{{cite journal | vauthors = Bossy-Wetzel E, Bakiri L, Yaniv M | title = Induction of apoptosis by the transcription factor c-Jun | journal = The EMBO Journal | volume = 16 | issue = 7 | pages = 1695–709 | date = April 1997 | pmid = 9130714 | pmc = 1169773 | doi = 10.1093/emboj/16.7.1695 }}

It has been shown that AP-1 motif regulates tissue-specific genes through enhancer selection mechanism in fibroblasts. {{cite journal |vauthors=Vierbuchen T, Ling E, Cowley CJ, Couch CH, Wang X, Harmin DA, Roberts CW, Greenberg ME |title=AP-1 Transcription Factors and the BAF Complex Mediate Signal-Dependent Enhancer Selection |journal=Mol Cell |volume=68 |issue=6 |pages=1067–1082.e12 |date=December 2017 |pmid=29272704 |pmc=5744881 |doi=10.1016/j.molcel.2017.11.026 }}

It has been shown that AP-1 motif is related to epigenetic regulation in kidney function {{cite journal |vauthors=Sagy N, Meyrom N, Beckerman P, Pleniceanu O, Bar DZ |title=Kidney-specific methylation patterns correlate with kidney function and are lost upon kidney disease progression |journal=Clin Epigenetics |volume=16 |issue=1 |pages=27 |date=February 2024 |pmid=38347603 |pmc=10863297 |doi=10.1186/s13148-024-01642-w |doi-access=free}} and now there is suspect that AP-1 motif is regulated in developing RPE, specifically through OTX2.{{cn|date=December 2024}}

Increased AP-1 levels lead to increased transactivation of target gene expression. Regulation of AP-1 activity is therefore critical for cell function and occurs through specific interactions controlled by dimer-composition, transcriptional and post-translational events, and interaction with accessory proteins.{{cite journal | vauthors = Vesely PW, Staber PB, Hoefler G, Kenner L | title = Translational regulation mechanisms of AP-1 proteins | journal = Mutation Research | volume = 682 | issue = 1 | pages = 7–12 | date = July 2009 | pmid = 19167516 | doi = 10.1016/j.mrrev.2009.01.001 | bibcode = 2009MRRMR.682....7V }}

AP-1 functions are heavily dependent on the specific Fos and Jun subunits contributing to AP-1 dimers. The outcome of AP-1 activation is dependent on the complex combinatorial patterns of AP-1 component dimers. The AP-1 complex binds to a palindromic DNA motif (5’-TGA G/C TCA-3’) to regulate gene expression, but specificity is dependent on the dimer composition of the bZIP subunit.

AP-1 transcription factor has been shown to be involved in skin physiology, specifically in tissue regeneration. The process of skin metabolism is initiated by signals that trigger undifferentiated proliferative cells to undergo cell differentiation. Therefore, activity of AP-1 subunits in response to extracellular signals may be modified under conditions where the balance of keratinocyte proliferation and differentiation has to be rapidly and temporally altered.{{cite journal | vauthors = Angel P, Szabowski A, Schorpp-Kistner M | title = Function and regulation of AP-1 subunits in skin physiology and pathology | journal = Oncogene | volume = 20 | issue = 19 | pages = 2413–23 | date = April 2001 | pmid = 11402337 | doi = 10.1038/sj.onc.1204380 | doi-access = free }}

The AP-1 transcription factor also has been shown to be involved in breast cancer cell growth through multiple mechanisms, including regulation of cyclin D1, E2F factors and their target genes. c-Jun, which is one of the AP-1 subunits, regulates the growth of breast cancer cells. Activated c-Jun is predominantly expressed at the invasive front in breast cancer and is associated with proliferation of breast cells.{{cite journal | vauthors = Shen Q, Uray IP, Li Y, Krisko TI, Strecker TE, Kim HT, Brown PH | title = The AP-1 transcription factor regulates breast cancer cell growth via cyclins and E2F factors | journal = Oncogene | volume = 27 | issue = 3 | pages = 366–77 | date = January 2008 | pmid = 17637753 | doi = 10.1038/sj.onc.1210643 | doi-access = free }} Due to the AP-1 regulatory functions in cancer cells, AP-1 modulation is studied as a potential strategy for cancer prevention and therapy.{{cite journal | vauthors = Eferl R, Wagner EF | title = AP-1: a double-edged sword in tumorigenesis | journal = Nature Reviews. Cancer | volume = 3 | issue = 11 | pages = 859–68 | date = November 2003 | pmid = 14668816 | doi = 10.1038/nrc1209 | s2cid = 35328722 }}{{cite journal | vauthors = Tewari D, Nabavi SF, Nabavi SM, Sureda A, Farooqi AA, Atanasov AG, Vacca RA, Sethi G, Bishayee A | title = Targeting activator protein 1 signaling pathway by bioactive natural agents: Possible therapeutic strategy for cancer prevention and intervention | journal = Pharmacological Research | volume = 128 | pages = 366–375 | date = February 2018 | pmid = 28951297 | doi = 10.1016/j.phrs.2017.09.014 | s2cid = 20160666 }}{{cite journal | vauthors = Kamide D, Yamashita T, Araki K, Tomifuji M, Tanaka Y, Tanaka S, Shiozawa S, Shiotani A | title = Selective activator protein-1 inhibitor T-5224 prevents lymph node metastasis in an oral cancer model | journal = Cancer Science | volume = 107 | issue = 5 | pages = 666–73 | date = May 2016 | pmid = 26918517 | pmc = 4970834 | doi = 10.1111/cas.12914 }}

{{Regulome

| activates = cAMP,{{cite journal | vauthors = Proffitt J, Crabtree G, Grove M, Daubersies P, Bailleul B, Wright E, Plumb M | title = An ATF/CREB-binding site is essential for cell-specific and inducible transcription of the murine MIP-1 beta cytokine gene | journal = Gene | volume = 152 | issue = 2 | pages = 173–9 | date = January 1995 | pmid = 7835696 | doi = 10.1016/0378-1119(94)00701-S }} IL-2,{{cite journal | vauthors = Rainio EM, Sandholm J, Koskinen PJ | title = Cutting edge: Transcriptional activity of NFATc1 is enhanced by the Pim-1 kinase | journal = Journal of Immunology | volume = 168 | issue = 4 | pages = 1524–7 | date = February 2002 | pmid = 11823475 | doi = 10.4049/jimmunol.168.4.1524 | doi-access = free }} CREB,{{cite journal | vauthors = Sanyal S, Sandstrom DJ, Hoeffer CA, Ramaswami M | title = AP-1 functions upstream of CREB to control synaptic plasticity in Drosophila | journal = Nature | volume = 416 | issue = 6883 | pages = 870–4 | date = April 2002 | pmid = 11976688 | doi = 10.1038/416870a | bibcode = 2002Natur.416..870S | s2cid = 4329320 }} WEE1,{{cite journal | vauthors = Hirayama J, Cardone L, Doi M, Sassone-Corsi P | title = Common pathways in circadian and cell cycle clocks: light-dependent activation of Fos/AP-1 in zebrafish controls CRY-1a and WEE-1 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 29 | pages = 10194–9 | date = July 2005 | pmid = 16000406 | pmc = 1177375 | doi = 10.1073/pnas.0502610102 | bibcode = 2005PNAS..10210194H | doi-access = free }} OPN,{{cite journal | vauthors = Wai PY, Mi Z, Gao C, Guo H, Marroquin C, Kuo PC | title = Ets-1 and runx2 regulate transcription of a metastatic gene, osteopontin, in murine colorectal cancer cells | journal = The Journal of Biological Chemistry | volume = 281 | issue = 28 | pages = 18973–82 | date = July 2006 | pmid = 16670084 | doi = 10.1074/jbc.M511962200 | doi-access = free }} RD,{{cite journal | vauthors = 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inhibits activation of the cyclin D1 and cyclin E kinase complexes | journal = Molecular Biology of the Cell | volume = 12 | issue = 8 | pages = 2352–63 | date = August 2001 | pmid = 11514621 | pmc = 58599 | doi = 10.1091/mbc.12.8.2352 | doi-access = free }} BMP-4,{{cite journal | vauthors = Knöchel S, Schuler-Metz A, Knöchel W | title = c-Jun (AP-1) activates BMP-4 transcription in Xenopus embryos | journal = Mechanisms of Development | volume = 98 | issue = 1–2 | pages = 29–36 | date = November 2000 | pmid = 11044605 | doi = 10.1016/S0925-4773(00)00448-2 | s2cid = 18150052 | doi-access = free }} H1 receptor,{{cite journal | vauthors = Kidd M, Hinoue T, Eick G, Lye KD, Mane SM, Wen Y, Modlin IM | title = Global expression analysis of ECL cells in Mastomys natalensis gastric mucosa identifies alterations in the AP-1 pathway induced by gastrin-mediated transformation | journal = Physiological Genomics | volume = 20 | issue = 1 | pages = 131–42 | date = December 2004 | pmid = 15602048 | doi = 10.1152/physiolgenomics.00216.2003 }} cyclin D1, GC-A,{{cite journal | vauthors = Heim JM, Singh S, Fülle HJ, Gerzer R | title = Comparison of a cloned ANF-sensitive guanylate cyclase (GC-A) with particulate guanylate cyclase from adrenal cortex | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 345 | issue = 1 | pages = 64–70 | date = January 1992 | pmid = 1347156 | doi = 10.1007/BF00175471 | s2cid = 22605840 }} TGF-b,{{cite journal | vauthors = Kuo YR, Wu WS, Wang FS | title = Flashlamp pulsed-dye laser suppressed TGF-beta1 expression and proliferation in cultured keloid fibroblasts is mediated by MAPK pathway | journal = Lasers in Surgery and Medicine | volume = 39 | issue = 4 | pages = 358–64 | date = April 2007 | pmid = 17457842 | doi = 10.1002/lsm.20489 | s2cid = 25556684 }} NOTCH4,{{cite journal | vauthors = Wu J, Bresnick EH | title = Glucocorticoid and growth factor synergism requirement for Notch4 chromatin domain activation | journal = Molecular and Cellular Biology | volume = 27 | issue = 6 | pages = 2411–22 | date = March 2007 | pmid = 17220278 | pmc = 1820485 | doi = 10.1128/MCB.02152-06 }} Blimp-1,{{cite journal | vauthors = Martins G, Calame K | title = Regulation and functions of Blimp-1 in T and B lymphocytes | journal = Annual Review of Immunology | volume = 26 | pages = 133–69 | year = 2008 | pmid = 18370921 | doi = 10.1146/annurev.immunol.26.021607.090241 }} FasL,{{Citation needed|date=June 2008}} TNF-a,{{Citation needed|date=June 2008}} c-jun,{{cite journal | vauthors = Lunec J, Holloway K, Cooke M, Evans M | title = Redox-regulation of DNA repair | journal = BioFactors | volume = 17 | issue = 1–4 | pages = 315–24 | year = 2003 | pmid = 12897453 | doi = 10.1002/biof.5520170131 | s2cid = 30654477 }} Bcl-xl,{{cite journal | vauthors = Manicassamy S, Gupta S, Huang Z, Sun Z | title = Protein kinase C-theta-mediated signals enhance CD4+ T cell survival by up-regulating Bcl-xL | journal = Journal of Immunology | volume = 176 | issue = 11 | pages = 6709–16 | date = June 2006 | pmid = 16709830 | doi = 10.4049/jimmunol.176.11.6709 | doi-access = free }} ECs,{{cite journal | vauthors = Wang N, Verna L, Hardy S, Forsayeth J, Zhu Y, Stemerman MB | title = Adenovirus-mediated overexpression of c-Jun and c-Fos induces intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 in human endothelial cells | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 19 | issue = 9 | pages = 2078–84 | date = September 1999 | pmid = 10479648 | doi = 10.1161/01.ATV.19.9.2078 | doi-access = free }} miR-21,{{cite journal | vauthors = Fujita S, Ito T, Mizutani T, Minoguchi S, Yamamichi N, Sakurai K, Iba H | title = miR-21 Gene expression triggered by AP-1 is sustained through a double-negative feedback mechanism | journal = Journal of Molecular Biology | volume = 378 | issue = 3 | pages = 492–504 | date = May 2008 | pmid = 18384814 | doi = 10.1016/j.jmb.2008.03.015 }} Cox-2,{{cite journal | vauthors = von Knethen A, Callsen D, Brüne B | title = NF-kappaB and AP-1 activation by nitric oxide attenuated apoptotic cell death in RAW 264.7 macrophages | journal = Molecular Biology of the Cell | volume = 10 | issue = 2 | pages = 361–72 | date = February 1999 | pmid = 9950682 | pmc = 25174 | doi = 10.1091/mbc.10.2.361 }} PtdIns(3,5)P2,{{cite journal | vauthors = Phelan JP, Millson SH, Parker PJ, Piper PW, Cooke FT | title = Fab1p and AP-1 are required for trafficking of endogenously ubiquitylated cargoes to the vacuole lumen in S. cerevisiae | journal = Journal of Cell Science | volume = 119 | issue = Pt 20 | pages = 4225–34 | date = October 2006 | pmid = 17003107 | doi = 10.1242/jcs.03188 | doi-access = free }} tissue factor,{{cite journal | vauthors = Nolasco LH, Turner NA, Bernardo A, Tao Z, Cleary TG, Dong JF, Moake JL | title = Hemolytic uremic syndrome-associated Shiga toxins promote endothelial-cell secretion and impair ADAMTS13 cleavage of unusually large von Willebrand 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The American Journal of Physiology | volume = 276 | issue = 5 Pt 2 | pages = F684–90 | date = May 1999 | pmid = 10330050 | doi = 10.1152/ajprenal.1999.276.5.F684 | doi-access = free }} IL-8,{{cite journal | vauthors = Stark CJ, Atreya CD | title = Molecular advances in the cell biology of SARS-CoV and current disease prevention strategies | journal = Virology Journal | volume = 2 | pages = 35 | date = April 2005 | pmid = 15833113 | pmc = 1087510 | doi = 10.1186/1743-422X-2-35 | doi-access = free }} IL-4,{{cite journal | vauthors = Lane SJ, Adcock IM, Richards D, Hawrylowicz C, Barnes PJ, Lee TH | title = Corticosteroid-resistant bronchial asthma is associated with increased c-fos expression in monocytes and T lymphocytes | journal = The Journal of Clinical Investigation | volume = 102 | issue = 12 | pages = 2156–64 | date = December 1998 | pmid = 9854051 | pmc = 509170 | doi = 10.1172/JCI2680 }} IL-5, GM-CSF, hGSTP1,{{cite journal | vauthors = Steiner C, Peters WH, Gallagher EP, Magee P, Rowland I, Pool-Zobel BL | title = Genistein protects human mammary epithelial cells from benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide and 4-hydroxy-2-nonenal genotoxicity by modulating the glutathione/glutathione S-transferase system | journal = Carcinogenesis | volume = 28 | issue = 3 | pages = 738–48 | date = March 2007 | pmid = 17065199 | doi = 10.1093/carcin/bgl180 | doi-access = free }} Egr-1,{{Citation needed|date=November 2015}} Fibronectin,{{Citation needed|date=November 2015}}

| inhibits = PAI-1,{{cite journal | vauthors = Ahn JD, Morishita R, Kaneda Y, Lee KU, Park JY, Jeon YJ, Song HS, Lee IK | title = Transcription factor decoy for activator protein-1 (AP-1) inhibits high glucose- and angiotensin II-induced type 1 plasminogen activator inhibitor (PAI-1) gene expression in cultured human vascular smooth muscle cells | journal = Diabetologia | volume = 44 | issue = 6 | pages = 713–20 | date = June 2001 | pmid = 11440364 | doi = 10.1007/s001250051680 | doi-access = free }} Collagen,{{cite journal | vauthors = Kang S, Fisher GJ, Voorhees JJ | title = Photoaging: pathogenesis, prevention, and treatment | journal = Clinics in Geriatric Medicine | volume = 17 | issue = 4 | pages = 643–59, v–vi | date = November 2001 | pmid = 11535421 | doi = 10.1016/S0749-0690(05)70091-4 }} HNF-1,{{cite journal | vauthors = Navasa M, Gordon DA, Hariharan N, Jamil H, Shigenaga JK, Moser A, Fiers W, Pollock A, Grunfeld C, Feingold KR | title = Regulation of microsomal triglyceride transfer protein mRNA expression by endotoxin and cytokines | journal = Journal of Lipid Research | volume = 39 | issue = 6 | pages = 1220–30 | date = June 1998 | doi = 10.1016/S0022-2275(20)32546-3 | pmid = 9643353 | url = http://www.jlr.org/content/39/6/1220.long | doi-access = free }} Osteocalcin,{{cite journal | vauthors = Suetsugu M, Takano A, Nagai A, Takeshita A, Hirose K, Matsumoto K, Sugiyama T, Kono S, Kawamata F, Satou T, Matsumoto M | display-authors = 6 | title=Retinoic acid inhibits serum-stimulated activator protein-1 via suppression of c-fos and c-jun gene expressions during the vitamin-induced differentiation of mouse osteoblastic cell line MC3T3-E1 cells |journal=J. Meikai Dent. Med. |date=2007 |volume=36 |issue=1 |pages=42–50 |url=http://www.dent.meikai.ac.jp/media/library/new-journals/2007_V36/42-50.pdf }}

| activated_by = PDTC,{{cite journal | vauthors = Inagi R, Miyata T, Nangaku M, Ueyama H, Takeyama K, Kato S, Kurokawa K | title = Transcriptional regulation of a mesangium-predominant gene, megsin | journal = Journal of the American Society of Nephrology | volume = 13 | issue = 11 | pages = 2715–22 | date = November 2002 | pmid = 12397041 | doi = 10.1097/01.ASN.0000033507.32175.FA | doi-access = free }} IE1,{{cite journal | vauthors = Kim S, Yu SS, Lee IS, Ohno S, Yim J, Kim S, Kang HS | title = Human cytomegalovirus IE1 protein activates AP-1 through a cellular protein kinase(s) | journal = The Journal of General Virology | volume = 80 ( Pt 4) | issue = 4 | pages = 961–9 | date = April 1999 | pmid = 10211966 | doi = 10.1099/0022-1317-80-4-961 | doi-access = free }} JNK,{{cite journal | vauthors = Masuda A, Yoshikai Y, Kume H, Matsuguchi T | title = The interaction between GATA proteins and activator protein-1 promotes the transcription of IL-13 in mast cells | journal = Journal of Immunology | volume = 173 | issue = 9 | pages = 5564–73 | date = November 2004 | pmid = 15494506 | doi = 10.4049/jimmunol.173.9.5564 | doi-access = free }} RIP2,{{cite journal | vauthors = Navas TA, Baldwin DT, Stewart TA | title = RIP2 is a Raf1-activated mitogen-activated protein kinase kinase | journal = The Journal of Biological Chemistry | volume = 274 | issue = 47 | pages = 33684–90 | date = November 1999 | pmid = 10559258 | doi = 10.1074/jbc.274.47.33684 | doi-access = free }} TPA,{{cite journal | vauthors = Simantov R | title = Neurotransporters: regulation, involvement in neurotoxicity, and the usefulness of antisense nucleic acids | journal = Biochemical Pharmacology | volume = 50 | issue = 4 | pages = 435–42 | date = August 1995 | pmid = 7646547 | doi = 10.1016/0006-2952(95)00068-B }} PDCD4,{{cite journal | vauthors = Yang HS, Jansen AP, Nair R, Shibahara K, Verma AK, Cmarik JL, Colburn NH | title = A novel transformation suppressor, Pdcd4, inhibits AP-1 transactivation but not NF-kappaB or ODC transactivation | journal = Oncogene | volume = 20 | issue = 6 | pages = 669–76 | date = February 2001 | pmid = 11314000 | doi = 10.1038/sj.onc.1204137 | doi-access = free }} KSHV,{{cite journal | vauthors = Xie J, Pan H, Yoo S, Gao SJ | title = Kaposi's sarcoma-associated herpesvirus induction of AP-1 and interleukin 6 during primary infection mediated by multiple mitogen-activated protein kinase pathways | journal = Journal of Virology | volume = 79 | issue = 24 | pages = 15027–37 | date = December 2005 | pmid = 16306573 | pmc = 1316010 | doi = 10.1128/JVI.79.24.15027-15037.2005 }} MAPK,{{cite journal | vauthors = Khan MA, Bouzari S, Ma C, Rosenberger CM, Bergstrom KS, Gibson DL, Steiner TS, Vallance BA | title = Flagellin-dependent and -independent inflammatory responses following infection by enteropathogenic Escherichia coli and Citrobacter rodentium | journal = Infection and Immunity | volume = 76 | issue = 4 | pages = 1410–22 | date = April 2008 | pmid = 18227166 | pmc = 2292885 | doi = 10.1128/IAI.01141-07 }} Serralysin,{{cite journal | vauthors = Kida Y, Inoue H, Shimizu T, Kuwano K | title = Serratia marcescens serralysin induces inflammatory responses through protease-activated receptor 2 | journal = Infection and Immunity | volume = 75 | issue = 1 | pages = 164–74 | date = January 2007 | pmid = 17043106 | pmc = 1828393 | doi = 10.1128/IAI.01239-06 }} PRL,{{cite journal | vauthors = Gutzman JH, Rugowski DE, Schroeder MD, Watters JJ, Schuler LA | title = Multiple kinase cascades mediate prolactin signals to activating protein-1 in breast cancer cells | journal = Molecular Endocrinology | volume = 18 | issue = 12 | pages = 3064–75 | date = December 2004 | pmid = 15319452 | pmc = 1634796 | doi = 10.1210/me.2004-0187 }} K15,{{cite journal | vauthors = Brinkmann MM, Glenn M, Rainbow L, Kieser A, Henke-Gendo C, Schulz TF | title = Activation of mitogen-activated protein kinase and NF-kappaB pathways by a Kaposi's sarcoma-associated herpesvirus K15 membrane protein | journal = Journal of Virology | volume = 77 | issue = 17 | pages = 9346–58 | date = September 2003 | pmid = 12915550 | pmc = 187392 | doi = 10.1128/JVI.77.17.9346-9358.2003 | doi-access = free }} Alpha lipoic acid,{{Citation needed|date=November 2015}} Phorbol esters,{{cite journal | vauthors = Greenstein S, Ghias K, Krett NL, Rosen ST | title = Mechanisms of glucocorticoid-mediated apoptosis in hematological malignancies | journal = Clinical Cancer Research | volume = 8 | issue = 6 | pages = 1681–94 | date = June 2002 | pmid = 12060604 | url = http://clincancerres.aacrjournals.org/content/8/6/1681.long }} Cytokine,{{cite journal | vauthors = Yokoo T, Kitamura M | title = Antioxidant PDTC induces stromelysin expression in mesangial cells via a tyrosine kinase-AP-1 pathway | journal = The American Journal of Physiology | volume = 270 | issue = 5 Pt 2 | pages = F806–11 | date = May 1996 | pmid = 8928842 | doi = 10.1152/ajprenal.1996.270.5.F806 }}

| inhibited_by = MIF,{{cite journal | vauthors = Chang CF, Cho S, Wang J | title = (-)-Epicatechin protects hemorrhagic brain via synergistic Nrf2 pathways | journal = Annals of Clinical and Translational Neurology | volume = 1 | issue = 4 | pages = 258–271 | date = April 2014 | pmid = 24741667 | pmc = 3984761 | doi = 10.1002/acn3.54 }}{{cite journal | vauthors = Gibbings DJ, Ghetu AF, Dery R, Befus AD | title = Macrophage migration inhibitory factor has a MHC class I-like motif and function | journal = Scandinavian Journal of Immunology | volume = 67 | issue = 2 | pages = 121–32 | date = February 2008 | pmid = 18201367 | doi = 10.1111/j.1365-3083.2007.02046.x | doi-access = free }} BATF[https://www.uniprot.org/uniprot/P05412 Uniprot Database] Ergothioneine{{cite journal | vauthors = Hseu YC, Vudhya Gowrisankar Y, Chen XZ, Yang YC, Yang HL | title = The antiaging activity of ergothioneine in UVA-irradiated human dermal fibroblasts via the inhibition of the AP-1 pathway and the activation of Nrf2-mediated antioxidant genes | journal = Oxid Med Cell Longev | volume = 2020 | issue = 2576823 | pages = 1–13| date = Feb 2020 | pmid = 32104530 | pmc = 7038158 | doi = 10.1155/2020/2576823 | doi-access = free }}

}}

• Activator protein
• Immediate early genes – Genes that are rapidly expressed in response to varied stimuli, without needing new proteins to be synthesized, including c-fos and c-jun{{cite journal|vauthors=Bahrami S, Drabløs F|title=Gene regulation in the immediate-early response process|journal=Advances in Biological Regulation|volume=62|year=2016|pages=37–49|pmid=27220739|doi=10.1016/j.jbior.2016.05.001|doi-access=free}}
• Transcription factor

{{reflist|30em}}

• [https://www.nlm.nih.gov/cgi/mesh/2008/MB_cgi?mode=&term=Transcription+Factor+AP-1 NLM]
• [https://web.archive.org/web/20151004234629/http://www.nlm.nih.gov/cgi/mesh/2008/MB_cgi Genecards]
• [http://atlasgeneticsoncology.org/Genes/JUNID151.html Atlas of Genetics]

{{Oncogenes}}

{{Transcription factors|g1}}

Category:Transcription factors