WAC Promotes Polo-like Kinase 1 Activation for Timely Mitotic Entry

WAC Promotes Polo-like Kinase 1 Activation for Timely Mitotic Entry
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WAC 促进 Polo 样激酶 1 激活以及时进入有丝分裂

DOI:
10.1016/j.celrep.2018.06.087
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发表时间:
2018-07-17
期刊:
影响因子:
8.8
通讯作者:
Wang, Fangwei
Wang, Fangwei
中科院分区:
生物学1区
文献类型:
--
作者:
Qi, Feifei;Chen, Qinfu;Wang, Fangwei

文献摘要

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The key mitotic regulator Polo-like kinase 1 (Plk1) is activated during G2 phase by Aurora A kinase (AurkA)-mediated phosphorylation of its activation loop, which is important for timely mitotic entry. The mechanism for Plk1 activation remains incompletely understood. Here, we report that the activation of Plk1 requires WAC, a WW domain-containing adaptor protein with a coiled-coil region that predominantly localizes to the nucleus in interphase. Cyclin-dependent kinase 1 (Cdk1) phosphorylates WAC, priming its direct interaction with the polo-box domain of Plk1. Knockdown of WAC compromises Plk1 activity and delays mitotic entry. These defects are rescued by exogenous expression of wild-type WAC, but not the Plk1-binding-deficient mutant. WAC also binds AurkA and can enhance Plk1 phosphorylation by AurkA in vitro. Taken together, these results indicate an important role for WAC in promoting Plk1 activation and the timely entry into mitosis.