Monday 19 May 2008
PPM1D is an oncogene that is amplified and overexpressed in many human tumors, including breast cancer.
It functions as a negative regulator of the p38 MAP kinase-p53 signaling pathway and is also proposed to participate in other critical cell survival pathways.
PPM1D is involved in the regulation of cell proliferation in breast cancer in a p53-dependent manner. Overexpression of PPM1D contributes to malignant phenotype by promoting sustained cell growth and cell survival.
- Exposure of mammalian cells to ionizing radiation (IR) induces a complex array of cellular responses, including cell cycle arrest and/or apoptosis. IR-induced G1 arrest has been shown to depend on the presence of the tumor suppressor p53 (TP53) (MIM.191170), which acts as a transcriptional activator of several genes.
- p53 also plays a role in the induction of apoptosis in response to DNA damage, and this pathway can be activated by both transcription-dependent and -independent mechanisms.
Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer. Ruark E, Snape K, Humburg P, Loveday C, Bajrami I, Brough R, Rodrigues DN, Renwick A, Seal S, Ramsay E, Duarte SD, Rivas MA, Warren-Perry M, Zachariou A, Campion-Flora A, Hanks S, Murray A, Pour NA, Douglas J, Gregory L, Rimmer A, Walker NM, Yang TP, Adlard JW, Barwell J, Berg J, Brady AF, Brewer C, Brice G, Chapman C, Cook J, Davidson R, Donaldson A, Douglas F, Eccles D, Evans DG, Greenhalgh L, Henderson A, Izatt L, Kumar A, Lalloo F, Miedzybrodzka Z, Morrison PJ, Paterson J, Porteous M, Rogers MT, Shanley S, Walker L, Gore M, Houlston R, Brown MA, Caufield MJ, Deloukas P, McCarthy MI, Todd JA; The Breast and Ovarian Cancer Susceptibility Collaboration; Wellcome Trust Case Control Consortium, Turnbull C, Reis-Filho JS, Ashworth A, Antoniou AC, Lord CJ, Donnelly P, Rahman N. Nature. 2012 Dec 16. doi : 10.1038/nature11725 PMID: 23242139
Pärssinen J, Alarmo EL, Karhu R, Kallioniemi A. PPM1D silencing by RNA interference inhibits proliferation and induces apoptosis in breast cancer cell lines with wild-type p53. Cancer Genet Cytogenet. 2008 Apr 1;182(1):33-9. PMID: 18328948