A node between proliferation, apoptosis, and growth arrest

Paradoxically, oncogenes and growth factors can induce proliferation and pr omote cellular survival but can also cause apoptosis and growth arrest. Wha t determines whether a cell decides to proliferate, arrest growth, or die? Mitogens and activators of mitogen-activated pathways initiate the simultan eous production of proliferative (cyclins) and anti-proliferative (CDK inhi bitors such as p21WAF1/ CIP1) signals. Quiescent cells may respond to these signals by proliferation whereas proliferating cells may respond by growth arrest. Although pro-apoptotic oncoproteins, which constitute the downstre am pathway (cyclin D, E2F, c-myc) directly induce proliferation, the activa tion of the upstream steps (growth factor receptors, Ras, cytoplasmic kinas es) is required to prevent apoptosis. BioEssays 21,704-709, 1999. (C) 1999 John Wiley & Sons, Inc.