Gain-of-Function p53N236S Mutation Drives the Bypassing of HRas^V12-Induced Cellular Senescence via PGC-1α.

ABSTRACT: One of the key steps in tumorigenic transformation is immortalization in which cells bypass cancer-initiating barriers such as senescence. Senescence can be triggered by either telomere erosion or oncogenic stress (oncogene-induced senescence, OIS) and undergo p53- or Rb-dependent cell cycle arrest. The tumor suppressor p53 is mutated in 50% of human cancers. In this study, we generated p53N236S (p53S) mutant knock-in mice and observed that p53S heterozygous mouse embryonic fibroblasts (p53^S/+) escaped HRas^V12-induced senescence after subculture in vitro and formed tumors after subcutaneous injection into severe combined immune deficiency (SCID) mice. We found that p53S increased the level and nuclear translocation of PGC-1α in late-stage p53^S/+</

SUBMITTER: Yang H 

PROVIDER: S-EPMC9960896 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature