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PPM1D

{{Short description|Protein-coding gene in the species Homo sapiens}}

{{Infobox_gene}}

Protein phosphatase 1D is an enzyme that in humans is encoded by the PPM1D gene.{{cite journal |vauthors=Fiscella M, Zhang H, Fan S, Sakaguchi K, Shen S, Mercer WE, Vande Woude GF, O'Connor PM, Appella E | title = Wip1, a novel human protein phosphatase that is induced in response to ionizing radiation in a p53-dependent manner | journal = Proc Natl Acad Sci U S A | volume = 94 | issue = 12 | pages = 6048–53 |date=July 1997 | pmid = 9177166 | pmc = 20998 | doi =10.1073/pnas.94.12.6048 | bibcode =1997PNAS...94.6048F | doi-access = free }}{{cite web | title = Entrez Gene: PPM1D protein phosphatase 1D magnesium-dependent, delta isoform| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8493}}

The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. The expression of this gene is induced in a p53-dependent manner in response to various environmental stresses. While being induced by tumor suppressor protein TP53/p53, this phosphatase negatively regulates the activity of p38 MAP kinase (MAPK/p38) through which it reduces the phosphorylation of p53, and in turn suppresses p53-mediated transcription and apoptosis. This phosphatase thus mediates a feedback regulation of p38-p53 signaling that contributes to growth inhibition and the suppression of stress induced apoptosis. This gene is located in a chromosomal region known to be amplified in breast cancer. The amplification of this gene has been detected in both breast cancer cell line and primary breast tumors, which suggests a role of this gene in cancer development. Pathogenic variants in exons 5-6 in the PPM1D gene can cause the neurodevelopmental disorder known as Jansen-de Vries Syndrome (JdVS).{{Cite journal |last1=Wojcik |first1=Monica H |last2=Srivastava |first2=Siddharth |last3=Agrawal |first3=Pankaj B |last4=Balci |first4=Tugce B |last5=Callewaert |first5=Bert |last6=Calvo |first6=Pier Luigi |last7=Carli |first7=Diana |last8=Caudle |first8=Michelle |last9=Colaiacovo |first9=Samantha |last10=Cross |first10=Laura |last11=Demetriou |first11=Kalliope |last12=Drazba |first12=Katy |last13=Dutra-Clarke |first13=Marina |last14=Edwards |first14=Matthew |last15=Genetti |first15=Casie A |date=July 2023 |title=Jansen-DeVries Syndrome: Expansion of the PPM1D Clinical and Phenotypic Spectrum in 34 Families |journal=American Journal of Medical Genetics. Part A |volume=191 |issue=7 |pages=1900–1910 |doi=10.1002/ajmg.a.63226 |issn=1552-4825 |pmid=37183572|pmc=10330231 }}

Interactions

PPM1D has been shown to interact with CDC5L.{{cite journal |last=Ajuh |first=P |author2=Kuster B |author3=Panov K |author4=Zomerdijk J C |author5=Mann M |author6=Lamond A I |date=December 2000 |title=Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry |journal=EMBO J. |volume=19 |issue=23 |pages=6569–81 | issn = 0261-4189| pmid = 11101529 |doi = 10.1093/emboj/19.23.6569 |pmc=305846 }}

References

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Further reading

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  • {{cite journal |vauthors=Adams MD, Kerlavage AR, Fleischmann RD, etal |title=Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence. |journal=Nature |volume=377 |issue= 6547 Suppl |pages= 3–174 |year= 1995 |pmid= 7566098 |url=http://www.columbia.edu/itc/biology/pollack/w4065/client_edit/readings/nature377_3.pdf }}
  • {{cite journal |vauthors=Hirano K, Ito M, Hartshorne DJ |title=Interaction of the ribosomal protein, L5, with protein phosphatase type 1. |journal=J. Biol. Chem. |volume=270 |issue= 34 |pages= 19786–90 |year= 1995 |pmid= 7649987 |doi=10.1074/jbc.270.34.19786 |doi-access=free }}
  • {{cite journal |vauthors=Takekawa M, Adachi M, Nakahata A, etal |title=p53-inducible wip1 phosphatase mediates a negative feedback regulation of p38 MAPK-p53 signaling in response to UV radiation. |journal=EMBO J. |volume=19 |issue= 23 |pages= 6517–26 |year= 2001 |pmid= 11101524 |doi= 10.1093/emboj/19.23.6517 | pmc=305857 }}
  • {{cite journal |vauthors=Ajuh P, Kuster B, Panov K, etal |title=Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry. |journal=EMBO J. |volume=19 |issue= 23 |pages= 6569–81 |year= 2001 |pmid= 11101529 |doi= 10.1093/emboj/19.23.6569 | pmc=305846 }}
  • {{cite journal |vauthors=Choi J, Nannenga B, Demidov ON, etal |title=Mice deficient for the wild-type p53-induced phosphatase gene (Wip1) exhibit defects in reproductive organs, immune function, and cell cycle control. |journal=Mol. Cell. Biol. |volume=22 |issue= 4 |pages= 1094–105 |year= 2002 |pmid= 11809801 |doi=10.1128/MCB.22.4.1094-1105.2002 | pmc=134641 }}
  • {{cite journal |vauthors=Li J, Yang Y, Peng Y, etal |title=Oncogenic properties of PPM1D located within a breast cancer amplification epicenter at 17q23. |journal=Nat. Genet. |volume=31 |issue= 2 |pages= 133–4 |year= 2002 |pmid= 12021784 |doi= 10.1038/ng888 |s2cid=5750250 }}
  • {{cite journal |vauthors=Bulavin DV, Demidov ON, Saito S, etal |title=Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity. |journal=Nat. Genet. |volume=31 |issue= 2 |pages= 210–5 |year= 2002 |pmid= 12021785 |doi= 10.1038/ng894 |s2cid=30048056 }}
  • {{cite journal |vauthors=Morimoto H, Okamura H, Haneji T |title=Interaction of protein phosphatase 1 delta with nucleolin in human osteoblastic cells. |journal=J. Histochem. Cytochem. |volume=50 |issue= 9 |pages= 1187–93 |year= 2002 |pmid= 12185196 |doi= 10.1177/002215540205000905|doi-access=free }}
  • {{cite journal |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |bibcode=2002PNAS...9916899M |doi-access=free }}
  • {{cite journal |vauthors=Imabayashi H, Mori T, Gojo S, etal |title=Redifferentiation of dedifferentiated chondrocytes and chondrogenesis of human bone marrow stromal cells via chondrosphere formation with expression profiling by large-scale cDNA analysis. |journal=Exp. Cell Res. |volume=288 |issue= 1 |pages= 35–50 |year= 2003 |pmid= 12878157 |doi=10.1016/S0014-4827(03)00130-7 }}
  • {{cite journal | author=Bernards R |title=Wip-ing out cancer. |journal=Nat. Genet. |volume=36 |issue= 4 |pages= 319–20 |year= 2004 |pmid= 15054481 |doi= 10.1038/ng0404-319 |doi-access= free }}
  • {{cite journal |vauthors=Lu X, Bocangel D, Nannenga B, etal |title=The p53-induced oncogenic phosphatase PPM1D interacts with uracil DNA glycosylase and suppresses base excision repair. |journal=Mol. Cell |volume=15 |issue= 4 |pages= 621–34 |year= 2004 |pmid= 15327777 |doi= 10.1016/j.molcel.2004.08.007 |doi-access= free }}
  • {{cite journal |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 }}
  • {{cite journal |vauthors=Yamaguchi H, Minopoli G, Demidov ON, etal |title=Substrate specificity of the human protein phosphatase 2Cdelta, Wip1. |journal=Biochemistry |volume=44 |issue= 14 |pages= 5285–94 |year= 2005 |pmid= 15807522 |doi= 10.1021/bi0476634 }}
  • {{cite journal |vauthors=Lu X, Nannenga B, Donehower LA |title=PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints. |journal=Genes Dev. |volume=19 |issue= 10 |pages= 1162–74 |year= 2005 |pmid= 15870257 |doi= 10.1101/gad.1291305 | pmc=1132003 }}
  • {{cite journal |vauthors=Rual JF, Venkatesan K, Hao T, etal |title=Towards a proteome-scale map of the human protein-protein interaction network. |journal=Nature |volume=437 |issue= 7062 |pages= 1173–8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 |bibcode=2005Natur.437.1173R |s2cid=4427026 }}
  • {{cite journal |vauthors=Rauta J, Alarmo EL, Kauraniemi P, etal |title=The serine-threonine protein phosphatase PPM1D is frequently activated through amplification in aggressive primary breast tumours. |journal=Breast Cancer Res. Treat. |volume=95 |issue= 3 |pages= 257–63 |year= 2006 |pmid= 16254685 |doi= 10.1007/s10549-005-9017-7 |s2cid=9693018 }}
  • {{cite journal |vauthors=Fujimoto H, Onishi N, Kato N, etal |title=Regulation of the antioncogenic Chk2 kinase by the oncogenic Wip1 phosphatase. |journal=Cell Death Differ. |volume=13 |issue= 7 |pages= 1170–80 |year= 2006 |pmid= 16311512 |doi= 10.1038/sj.cdd.4401801 |doi-access= free }}
  • {{cite journal |vauthors=Mendrzyk F, Radlwimmer B, Joos S, etal |title=Genomic and protein expression profiling identifies CDK6 as novel independent prognostic marker in medulloblastoma. |journal=J. Clin. Oncol. |volume=23 |issue= 34 |pages= 8853–62 |year= 2006 |pmid= 16314645 |doi= 10.1200/JCO.2005.02.8589 }}

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