The Molecular Mechanisms of Cell Cycle Regulation by CDK4, DREAM, and Myb-MuvB Complexes

The Rb family (p130, p107 and Rb) are tumor suppressor proteins that are frequently inactivated in human cancers. p130 and p107 form the DREAM complex to regulate quiescence while Rb-E2F regulates G1 of the cell cycle. The Rb family prevents cell cycle entry and proliferation by suppressing E2F directed gene activation. The activation of cyclin dependent kinases following growth stimulation results in serine/threonine phosphorylation of the Rb proteins resulting in release of E2F. Following DREAM and Rb-E2F complex inactivation by CDK phosphorylation, E2F and the Myb-MuvB complex activate genes required for DNA synthesis and mitosis. This study focuses on the molecular mechanisms that CDKs and oncogenic viruses use to inactivate DREAM and Rb-E2F complexes to activate E2F and Myb-MuvB in cancer