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.
p53
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.
References
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