The PPARγ-SETD8 axis constitutes an epigenetic, p53-independent checkpoint on p21-mediated cellular senescence.

ABSTRACT: Cellular senescence is a permanent proliferative arrest triggered by genome instability or aberrant growth stresses, acting as a protective or even tumor-suppressive mechanism. While several key aspects of gene regulation have been known to program this cessation of cell growth, the involvement of the epigenetic regulation has just emerged but remains largely unresolved. Using a systems approach that is based on targeted gene profiling, we uncovered known and novel chromatin modifiers with putative link to the senescent state of the cells. Among these, we identified SETD8 as a new target as well as a key regulator of the cellular senescence signaling. Knockdown of SETD8 triggered senescence induction in proliferative culture, irrespectively of the p53 status of the cells; ectopic expressio

SUBMITTER: Shih CT 

PROVIDER: S-EPMC5506440 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature