Cep85 Relays Plk1 Activity to Phosphorylated Nek2A for Its Timely Activation in Centrosome Disjunction
Cep85 Relays Plk1 Activity to Phosphorylated Nek2A for Its Timely Activation in Centrosome Disjunction
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Cep85 将 Plk1 活性传递给磷酸化 Nek2A，使其在中心体分离中及时激活
DOI：
10.1016/j.isci.2018.12.013
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发表时间：
2019-01-25
期刊：
影响因子：
5.8
通讯作者：
Yu, Xianwen
中科院分区：
文献类型：
--
作者：
Chen, Canhe;Xu, Zhenping;Yu, Xianwen
中心体的及时分离对染色体的准确分离至关重要。它在有丝分裂开始时由Nek 2A启动，但其自身激活严格需要磷酸化Nek 2A的机制仍不清楚。在这项研究中，我们发现Plkl 1与Cep 85相互作用，并与Cep 85-Nek 2A形成三元复合物。Nek 2A结合，而不是其激酶活性，是Cep 85被Plk 1磷酸化的先决条件。Nek 2A依赖性CepB 5磷酸化反过来导致磷酸化CepB 5仅从磷酸化Nek 2A解离，从而增加游离的磷酸化Nek 2A活性。这两种激酶也是磷酸化细胞中内源性Cep 85所必需的，并且CepB 5和Nek 2A的及时磷酸化对于在G2/M启动中心体分离至关重要。总的来说，我们的研究揭示了Plk 1和Nek 2A以前未被认识到的作用，并确定Cep 85作为一个缺失的片段，直接将Plk 1活性传递给Nek 2A，以激活中心体分离。
Timely centrosome separation is critical for accurate chromosome separation. It is initiated by Nek2A at the onset of mitosis, but the mechanism for the strict requirement of phosphorylated Nek2A for its own activation remains unclear. In this study, we have found that Plkl1 interacts with Cep85 and forms a ternary complex with Cep85-Nek2A. Nek2A binding, but not its kinase activity, is pre-required for Cep85 to be phosphorylated by Plk1. Nek2A-dependent CepB5 phosphorylation, in turn, leads to the dissociation of phosphorylated CepB5 exclusively from phospho-Nek2A, thereby increasing the freed phospho-Nek2A activity. Both kinases are also required for phosphorylating endogenous Cep85 in cells, and timely phosphorylation of CepB5 and Nek2A is crucial for initiating centrosome disjunction at G2/M. Overall, our study has uncovered a previously unrecognized role of Plk1 and Nek2A and identified Cep85 as a missing piece directly relaying Plk1 activity to Nek2A for its activation in centrosome disjunction.