A node between proliferation, apoptosis, and growth arrest.
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.
Blagosklonny
M V
MV
Medicine Branch, National Cancer Institute, Bldg. 10, R 12N226, NIH, Bethesda, Maryland 20892, USA. mikhailb@box-m.nih.gov
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D002455:Cell Division / Q000235:genetics / Q000502:physiology*; D018844:Cyclin-Dependent Kinases / Q000502:physiology; D016213:Cyclins / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D009857:Oncogenes; D015398:Signal Transduction
D016213:Cyclins; D018844:Cyclin-Dependent Kinases