Menssen R, Neutzner A, Seufert W
Institute of Industrial Genetics, University of Stuttgart, Stuttgart 70569, Germany.
Curr Biol. 2001 Mar 6;11(5):345-50. doi: 10.1016/s0960-9822(01)00095-1.
The inactivation of mitotic cyclin-dependent kinases (CDKs) during anaphase is a prerequisite for the completion of nuclear division and the onset of cytokinesis [1, 2]. In the budding yeast Saccharomyces cerevisiae, the essential protein kinase Cdc15 [3] together with other proteins of the mitotic exit network (Tem1, Lte1, Cdc5, and Dbf2/Dbf20 [4-7]) activates Cdc14 phosphatase, which triggers cyclin degradation and the accumulation of the CDK inhibitor Sic1 [8]. However, it is still unclear how CDK inactivation promotes cytokinesis. Here, we analyze the properties of Cdc15 kinase during mitotic exit. We found that Cdc15 localized to the spindle pole body (SPB) in a unique pattern. Cdc15 was present at the SPB of the mother cell until late mitosis, when it also associated with the daughter pole. High CDK activity inhibited this association, while dephosphorylation of Cdc15 by Cdc14 phosphatase enabled it. The analysis of Cdc15 derivatives indicated that SPB localization was specifically required for cytokinesis but not for mitotic exit. These results show that Cdc15 has two separate functions during the cell cycle. First, it is required for the activation of Cdc14. CD14, in turn, promotes CDK inactivation and also dephosphorylates of Cdc15. As a consequence, Cdc15 binds to the daughter pole and triggers cytokinesis. Thus, Cdc15 helps to coordinate mitotic exit and cytokinesis.
后期有丝分裂周期蛋白依赖性激酶（CDK）的失活是完成核分裂和启动胞质分裂的前提条件[1,2]。在芽殖酵母酿酒酵母中，必需的蛋白激酶Cdc15[3]与有丝分裂退出网络的其他蛋白（Tem1、Lte1、Cdc5和Dbf2/Dbf20[4-7]）一起激活Cdc14磷酸酶，后者触发周期蛋白降解和CDK抑制剂Sic1的积累[8]。然而，CDK失活如何促进胞质分裂仍不清楚。在这里，我们分析了有丝分裂退出过程中Cdc15激酶的特性。我们发现Cdc15以独特的模式定位于纺锤体极体（SPB）。Cdc15在母细胞的SPB上一直存在到有丝分裂后期，此时它也与子极相关联。高CDK活性抑制这种关联，而Cdc14磷酸酶对Cdc15的去磷酸化则使其能够发生这种关联。对Cdc15衍生物的分析表明，SPB定位是胞质分裂所特需的，但不是有丝分裂退出所必需的。这些结果表明，Cdc15在细胞周期中有两个独立的功能。首先，它是激活Cdc14所必需的。反过来，Cdc14促进CDK失活，并且也使Cdc15去磷酸化。结果，Cdc15与子极结合并触发胞质分裂。因此，Cdc15有助于协调有丝分裂退出和胞质分裂。
