Inactivation of cyclin-dependent kinases during exit from mitosis Inaktivierung Cyclin-abhängiger Kinasen beim Austritt aus der Mitose

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Cyclin-dependent kinases (Cdks) are key regulators of the eukaryotic cell division cycle. Their inactivation is required for completion of mitosis and entry into G1. Inactivation is primarily achieved by ubiquitin-mediated proteolysis of mitotic cyclins. In budding yeast, Hct1 cooperates with the anaphase promoting complex to ubiquitinate the mitotic cyclin Clb2. Sic1-mediated inhibition constitutes a parallel pathway for Cdk1 inactivation. A feedback loop governs Cdk1 inactivation since Hct1 and Sic1 are themselves inhibited by Cdk1 activity. It is largely unclear how Cdk1 inactivation is initiated and how this is integrated into the cellular processes during the M to G1 transition. To addresss these questions we will investigate functions of the protein kinase Cdc15 and the phosphatase Cdc14 which belong to a group of proteins needed for exit from mitosis. Among others we will characterize the subcellular localization of Cdc15 to address a potential link of cyclin proteolysis and spindle structure. Another important issue will be the regulation of Cdc14, specifically the role of Cdk1 and the polo-related kinase Cdc5.