title: Stop and go: anti-proliferative and mitogenic functions of the transcription factor C/EBPbeta.
abstract: Oncogene-induced senescence (OIS) is an irreversible form of cell cycle arrest that can be elicited by overexpression of oncogenes such as RasV12 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/EBPbeta, a downstream target of Ras signaling, is an essential component of RasV12-mediated senescence in mouse embryo fibroblasts (MEFs). C/EBPbeta induces cell cycle arrest through a mechanism requiring RB:E2F repressor complexes and negatively regulates several E2F target genes. Although C/EBPbeta has tumor suppressor-like activity in MEFs, other observations point to critical pro-oncogenic functions for C/EBPbeta in certain cancers. Here we review the evidence for positive and negative cell cycle regulation by C/EBPbeta and discuss possible mechanisms by which this transcription factor could participate in both cellular senescence and oncogenic transformation.
authors: Laboratory of Protein Dynamics and Signaling, NCI-Frederick, Frederick, Maryland 21702-1201, USA.
authors: Thomas
authors: T
authors: Sebastian
authors: Peter F
authors: PF
authors: Johnson