Neef Rüdiger, Gruneberg Ulrike, Kopajtich Robert, Li Xiuling, Nigg Erich A, Sillje Herman, Barr Francis A
Intracellular Protein Transport, Independent Junior Research Group, Max-Planck-Institute of Biochemistry, Martinsried, 82152 Germany.
Nat Cell Biol. 2007 Apr;9(4):436-44. doi: 10.1038/ncb1557. Epub 2007 Mar 11.
Spatial and temporal coordination of polo-like kinase 1 (Plk1) activity is necessary for mitosis and cytokinesis, and this is achieved through binding to phosphorylated docking proteins with distinct subcellular localizations. Although cyclin-dependent kinase 1 (Cdk1) creates these phosphorylated docking sites in metaphase, a general principle that explains how Plk1 activity is controlled in anaphase after Cdk1 inactivation is lacking. Here, we show that the microtubule-associated protein regulating cytokinesis (PRC1) is an anaphase-specific binding partner for Plk1, and that this interaction is required for cytokinesis. In anaphase, Plk1 creates its own docking site on PRC1, whereas in metaphase Cdk1 phosphorylates PRC1 adjacent to this docking site and thereby prevents binding of Plk1. Mutation of these Cdk1-sites results in a form of PRC1 that prematurely recruits Plk1 to the spindle during prometaphase and blocks mitotic progression. The activation state of Cdk1, therefore, controls the switch of Plk1 localization from centrosomes and kinetochores during metaphase, to the central spindle during anaphase.
Polo样激酶1(Plk1)活性的时空协调对于有丝分裂和胞质分裂是必需的,这是通过与具有不同亚细胞定位的磷酸化对接蛋白结合来实现的。尽管细胞周期蛋白依赖性激酶1(Cdk1)在中期产生这些磷酸化对接位点,但缺乏一个能解释Cdk1失活后后期Plk1活性如何被调控的一般原则。在这里,我们表明微管相关蛋白调节胞质分裂(PRC1)是Plk1在后期的特异性结合伴侣,并且这种相互作用是胞质分裂所必需的。在后期,Plk1在PRC1上创建自己的对接位点,而在中期Cdk1使该对接位点附近的PRC1磷酸化,从而阻止Plk1的结合。这些Cdk1位点的突变导致一种PRC1形式,其在前中期过早地将Plk1募集到纺锤体并阻断有丝分裂进程。因此,Cdk1的激活状态控制着Plk1定位从中期的中心体和动粒向后期的中央纺锤体的转变。