PPM1D

Protein phosphatase, Mg2+/Mn2+ dependent, 1D

Identifiers

PPM1D; PP2C-DELTA; WIP1

External IDs

OMIM: 605100 MGI: 1858214 HomoloGene: 31185 GeneCards: PPM1D Gene

3.1.3.16

Gene Ontology
Molecular function	• protein serine/threonine phosphatase activity • protein binding • hydrolase activity • metal ion binding
Cellular component	• nucleus • protein serine/threonine phosphatase complex
Biological process	• G2/M transition of mitotic cell cycle • protein dephosphorylation • cell cycle • negative regulation of cell proliferation • response to radiation • response to bacterium
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

n/a

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 17:
58.68 – 58.74 Mb

Chr 11:
85.12 – 85.16 Mb

PubMed search

[1]

[2]

Protein phosphatase 1D is an enzyme that in humans is encoded by the PPM1D gene.^[1]^[2]

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.^[2]

Interactions

PPM1D has been shown to interact with CDC5L.^[3]

References

^ Fiscella M, Zhang H, Fan S, Sakaguchi K, Shen S, Mercer WE, Vande Woude GF, O'Connor PM, Appella E (Jul 1997). "Wip1, a novel human protein phosphatase that is induced in response to ionizing radiation in a p53-dependent manner". Proc Natl Acad Sci U S A 94 (12): 6048–53. doi:10.1073/pnas.94.12.6048. PMC 20998. PMID 9177166. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=20998.
^ ^a ^b "Entrez Gene: PPM1D protein phosphatase 1D magnesium-dependent, delta isoform". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8493.
^ Ajuh, P; Kuster B, Panov K, Zomerdijk J C, Mann M, Lamond A I (Dec. 2000). "Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry". EMBO J. (ENGLAND) 19 (23): 6569–81. doi:10.1093/emboj/19.23.6569. ISSN 0261-4189. PMC 305846. PMID 11101529. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=305846.

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

PPM1D

Interactions

References

Further reading