C/EBPbeta cooperates with RB:E2F to implement Ras(V12)-induced cellular senescence.

ABSTRACT: In primary cells, overexpression of oncogenes such as Ras(V12) induces premature senescence rather than transformation. Senescence is an irreversible form of G1 arrest that requires the p19ARF/p53 and p16INK4a/pRB pathways and may suppress tumorigenesis in vivo. Here we show that the transcription factor C/EBPbeta is required for Ras(V12)-induced senescence. C/EBPbeta-/- mouse embryo fibroblasts (MEFs) expressing Ras(V12) continued to proliferate despite unimpaired induction of p19ARF and p53, and lacked morphological features of senescent fibroblasts. Enforced C/EBPbeta expression inhibited proliferation of wild-type MEFs and also slowed proliferation of p19Arf-/- and p53-/- cells, indicating that C/EBPbeta acts downstream or independently of p19ARF/p53 to suppress growth. C/EBPbeta was u

SUBMITTER: Sebastian T 

PROVIDER: S-EPMC1224679 | biostudies-literature | 2005 Sep

REPOSITORIES: biostudies-literature