Signaling Pathways that Control Cell Proliferation

Cells decide to proliferate or remain quiescent using signaling pathways that link information about the cellular environment to the G(1) phase of the cell cycle. Progression through G(1) phase is controlled by pRB proteins, which function to repress the activity of E2F transcription factors in cells exiting mitosis and in quiescent cells. Phosphorylation of pRB proteins by the G(1) cyclin-dependent kinases (CDKs) releases E2F factors, promoting the transition to S phase. CDK activity is primarily regulated by the binding of CDK catalytic subunits to cyclin partners and CDK inhibitors. Consequently, both mitogenic and antiproliferative signals exert their effects on cell proliferation through the transcriptional regulation and ubiquitin-dependent degradation of cyclins and CDK inhibitors.