HdmX overexpression inhibits oncogene induced cellular senescence.

ABSTRACT: Cellular senescence is an irreversible state of terminal growth arrest that requires functional p53. Acting to block tumor formation, induction of senescence has also been demonstrated to contribute to tumor clearance via the immune system following p53 reactivation. The Hdm2-antagonist, Nutlin-3a, has been shown to reactivate p53 and induce a quiescent state in various cancer cell lines, similar to the G(1) arrest observed upon RNAi targeting of Hdm2 in MCF7 breast cancer. In the present study we show that HdmX, a negative regulator of p53, impacts the senescence pathway. Specifically, overexpression of HdmX blocks Ras mediated senescence in primary human fibroblasts. The interaction of HdmX with p53 and the re-localization of HdmX to the nucleus through Hdm2 association appear to be requ

SUBMITTER: Miller KR 

PROVIDER: S-EPMC3041169 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature