Science · 1998 · 520 citations · 22 references
Life SciencesCell BiologyMolecular BiologyCell DivisionCellular BiochemistryMolecular Cell BiologyCell Cycle SignalingCell Cycle TransitionsCyclin-dependent KinasesMitosisProtein DegradationProtein Kinase CascadesAnaphase-promoting ComplexCyclin DegradationCyclin-dependent Kinase RegulationCyclinsE3 Ubiquitin Ligase Substrate RecognitionMitotic CyclinsProteolysis In Cell-cycle ControlUbiquitin-mediated Cell-cycle Regulation
Proteolysis of mitotic cyclins depends on a multisubunit ubiquitin-protein ligase, the anaphase promoting complex (APC). Proteolysis commences during anaphase, persisting throughout G1 until it is terminated by cyclin-dependent kinases (CDKs) as cells enter S phase. Proteolysis of mitotic cyclins in yeast was shown to require association of the APC with the substrate-specific activator Hct1 (also called Cdh1). Phosphorylation of Hct1 by CDKs blocked the Hct1-APC interaction. The mutual inhibition between APC and CDKs explains how cells suppress mitotic CDK activity during G1 and then establish a period with elevated kinase activity from S phase until anaphase.
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