Stop and go -: Anti-proliferative and mitogenic functions of the transcription factor C/EBPβ

Oncogene-induced senescence (OIS) is an irreversible form of cell cycle arrest that can be elicited by overexpression of oncogenes such as Ras(V12) and requires activation of the Arf-p53 and RB tumor suppressor pathways. Increasing evidence implicates senescence as a bona fide tumor suppression mechanism in vivo. We recently discovered that the bZIP transcription factor C/EBP beta, a downstream target of Ras signaling, is an essential component of Ras(V12)-mediated senescence in mouse embryo fibroblasts (MEFs). C/EBP beta induces cell cycle arrest through a mechanism requiring RB:E2F repressor complexes and negatively regulates several E2F target genes. Although C/EBP beta has tumor suppressor-like activity in MEFs, other observations point to critical pro-oncogenic functions for C/EBP beta in certain cancers. Here we review the evidence for positive and negative cell cycle regulation by C/EBP beta and discuss possible mechanisms by which this transcription factor could participate in both cellular senescence and oncogenic transformation.