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

细胞周期蛋白依赖性激酶（Cdks）是真核细胞分裂周期的关键调节因子。它们的失活是完成有丝分裂和进入G1所必需的。失活主要通过泛素介导的有丝分裂细胞周期蛋白的蛋白水解来实现。在芽殖酵母中，Hct 1与后期促进复合物合作，泛素化有丝分裂细胞周期蛋白Clb 2。Sic1介导的抑制构成了Cdk1失活的平行途径。一个反馈回路支配Cdk1失活，因为Hct1和Sic1本身被Cdk1活性抑制。目前还不清楚Cdk1的失活是如何启动的，以及在M到G1的转变过程中如何整合到细胞过程中。为了解决这些问题，我们将研究蛋白激酶Cdc15和磷酸酶Cdc14的功能，它们属于一组退出有丝分裂所需的蛋白质。其中，我们将描述Cdc15的亚细胞定位，以解决细胞周期蛋白水解和纺锤体结构的潜在联系。另一个重要的问题是Cdc14的调节，特别是Cdk1和polo相关激酶Cdc5的作用。

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.