Plk1 Controls the Nek2A-PP1γ Antagonism in Centrosome Disjunction
Plk1 Controls the Nek2A-PP1γ Antagonism in Centrosome Disjunction
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DOI：
10.1016/j.cub.2011.05.047
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发表时间：
2011-07-12
期刊：
影响因子：
9.2
通讯作者：
Schiebel, Elmar
中科院分区：
文献类型：
--
作者：
Mardin, Balca R.;Agircan, Fikret G.;Schiebel, Elmar
在人类细胞中，中心体的分离和双极纺锤体的形成对于正确的染色体分离是必不可少的[1]。在间期，中心体通过连接蛋白C-Nap 1和rootoke连接在一起[2-4]。在有丝分裂开始时，这些连接蛋白被磷酸化并被Nek 2A激酶从中心体置换，Nek 2A激酶由两个Hippo途径组分Mst 2激酶和支架蛋白hSav 1调节。驱动蛋白-5马达蛋白Eg 5以与Nek 2A平行的途径促进中心体分离[5]。在这里，我们报告Polo样激酶1（Plk 1）的功能上游的Mst 2-Nek 2A激酶模块在中心体分离，以及重要的Eg 5定位在中心体。Plk 1通过磷酸化Mst 2调节Mst 2-Nek 2A诱导的中心体分离。Mst 2的Plk 1磷酸化的缺乏促进Nek 2A-PP 1 γ-Mst 2复合物的组装，其中PP 1 γ抵消Nek 2A激酶活性。相反，Mst 2的Plk 1磷酸化阻止PP 1 γ与Mst 2-Nek 2A结合，从而允许Nek 2A活性促进中心体分离。我们建议，中心体分离调节Plk 1，提供了一个平衡的控制之间的抵消Nek 2A和PP 1 γ活动的中心体接头。
In human cells, separation of the centrosomes and formation of a bipolar spindle are essential for correct chromosome segregation [1]. During interphase, centrosomes are joined together by the linker proteins C-Nap1 and rootletin [2-4]. At the onset of mitosis, these linker proteins are phosphorylated and displaced from centrosomes by the Nek2A kinase, which is regulated by two Hippo pathway components, Mst2 kinase and the scaffold protein hSav1. The kinesin-5 motor protein Eg5 promotes centrosome separation in a parallel pathway to Nek2A [5]. Here, we report that Polo-like kinase 1 (Plk1) functions upstream of the Mst2-Nek2A kinase module in centrosome disjunction as well as being important for Eg5 localization at centrosomes. Plk1 regulates Mst2-Nek2A-induced centrosome disjunction by phosphorylating Mst2. The absence of Plk1 phosphorylation of Mst2 promotes assembly of Nek2A-PP1 gamma-Mst2 complexes, in which PP1 gamma counteracts Nek2A kinase activity. In contrast, Plk1 phosphorylation of Mst2 prevents PP1 gamma binding to Mst2-Nek2A, allowing Nek2A activity to promote centrosome disjunction. We propose that centrosome disjunction is regulated by Plk1, providing a well-balanced control between the counteracting Nek2A and PP1 gamma activities on the centrosome linker.