A node between proliferation, apoptosis, and growth arrest.

Abstract

Paradoxically, oncogenes and growth factors can induce proliferation and promote cellular survival but can also cause apoptosis and growth arrest. What determines whether a cell decides to proliferate, arrest growth, or die? Mitogens and activators of mitogen-activated pathways initiate the simultaneous production of proliferative (cyclins) and anti-proliferative (CDK inhibitors 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 downstream pathway (cyclin D, E2F, c-myc) directly induce proliferation, the activation of the upstream steps (growth factor receptors, Ras, cytoplasmic kinases) is required to prevent apoptosis.