PPM1D
Protein phosphatase 1D magnesium-dependent, delta isoform | |||||||||||
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Identifiers | |||||||||||
Symbols | PPM1D ; PP2C-DELTA; WIP1 | ||||||||||
External IDs | Template:OMIM5 Template:MGI HomoloGene: 31185 | ||||||||||
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RNA expression pattern | |||||||||||
File:PBB GE PPM1D 204566 at tn.png | |||||||||||
More reference expression data | |||||||||||
Orthologs | |||||||||||
Template:GNF Ortholog box | |||||||||||
Species | Human | Mouse | |||||||||
Entrez | n/a | n/a | |||||||||
Ensembl | n/a | n/a | |||||||||
UniProt | n/a | n/a | |||||||||
RefSeq (mRNA) | n/a | n/a | |||||||||
RefSeq (protein) | n/a | n/a | |||||||||
Location (UCSC) | n/a | n/a | |||||||||
PubMed search | n/a | n/a |
Protein phosphatase 1D magnesium-dependent, delta isoform, also known as PPM1D, is a human gene.[1]
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.[1]
References
Further reading
- 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". Nature. 377 (6547 Suppl): 3–174. PMID 7566098.
- 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. PMID 7649987.
- Fiscella M, Zhang H, Fan S; et al. (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. PMID 9177166.
- 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. PMID 11101524.
- 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. PMID 11101529.
- 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. PMID 11809801.
- 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. 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. PMID 12477932.
- 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. 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. PMID 15489334.
- 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. PMID 15870257.
- 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.
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