PPM1D
表示
Protein phosphatase 1D はヒトppm1d遺伝子によってコードされる酵素である[5][6]。
PPM1DはPPMファミリーに分類されるSer/Thrホスファターゼである。PPMファミリーは細胞ストレス応答経路のネガティブレギュレイターとして知られている。PPM1Dは、当初tumor suppressor protein TP53/p53依存的な様々な環境ストレスに応答して誘導されるホスファターゼとして同定された。p53やp38 MAPキナーゼ (MAPK/p38) の直接的な脱リン酸化によって、それらの活性を負に制御し、細胞周期停止やアポトーシスを抑制する。このことからp53のフィードバック制御因子であると考えられている。また、細胞周期制御因子の脱リン酸化によってp53非依存的に細胞周期を制御することが知られている。この遺伝子は乳癌由来細胞株および、初期乳癌組織において増幅が報告されており、このことは癌発生におけるppm1d遺伝子の役割を示唆している[6]。
相互作用
[編集]PPM1DはCDC5Lと相互作用することが報告されている[7]。
引用文献
[編集]- ^ a b c GRCh38: Ensembl release 89: ENSG00000170836 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020525 - Ensembl, May 2017
- ^ Human PubMed Reference:
- ^ Mouse PubMed Reference:
- ^ Fiscella M, Zhang H, Fan S, Sakaguchi K, Shen S, Mercer WE, Vande Woude GF, O'Connor PM, Appella E (July 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 .
- ^ a b “Entrez Gene: PPM1D protein phosphatase 1D magnesium-dependent, delta isoform”. 2014年7月9日閲覧。
- ^ Ajuh, P; Kuster B, Panov K, Zomerdijk J C, Mann M, Lamond A I (December 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 .
参考文献
[編集]- 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 .
- 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 .
- 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 .
- 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 .
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- 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.
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- 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 .
- 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 .
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- 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.