PLK1 Activation in Late G2 Sets Up Commitment to Mitosis
PLK1 Activation in Late G2 Sets Up Commitment to Mitosis
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DOI：
10.1016/j.celrep.2017.05.031
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发表时间：
2017-06-06
期刊：
影响因子：
8.8
通讯作者：
Gavet, Olivier
中科院分区：
文献类型：
--
作者：
Gheghiani, Lilia;Loew, Damarys;Gavet, Olivier
对有丝分裂的承诺必须与DNA复制紧密协调，以保持基因组的完整性。虽然我们之前已经证实，在G2晚期及时激活Cylin B1-CDK1会触发有丝分裂进入，但上游调控机制仍不清楚。在这里，我们报告了Polo-like kinase1(Plk1)是在一个不受干扰的细胞周期中进入有丝分裂所必需的，并且在CyclinB1-CDK1之前被迅速激活。我们确定Plk1与CDc25C1磷酸酶结合，并在有丝分裂进入之前诱导其磷酸化。PLK1依赖的CDC25C1亚磷酸盐足以促进有丝分裂进入，即使Plk1活性被抑制。此外，我们发现在G2期间Plk1的激活依赖于CyclinA2-CDK的活性水平。因此，我们的发现阐明了Plk1在Cyclin B1-CDK1激活和有丝分裂进入中的关键作用，并概述了Cyclin A2-CDK，一种S促进因子，是如何平衡细胞参与有丝分裂的。
Commitment to mitosis must be tightly coordinated with DNA replication to preserve genome integrity. While we have previously established that the timely activation of CyclinB1-Cdk1 in late G2 triggers mitotic entry, the upstream regulatory mechanisms remain unclear. Here, we report that Polo-like kinase 1 (Plk1) is required for entry into mitosis during an unperturbed cell cycle and is rapidly activated shortly before CyclinB1-Cdk1. We determine that Plk1 associates with the Cdc25C1 phosphatase and induces its phosphorylation beforemitotic entry. Plk1-dependent Cdc25C1 phosphosites are sufficient to promote mitotic entry, even when Plk1 activity is inhibited. Furthermore, we find that activation of Plk1 during G2 relies on CyclinA2-Cdk activity levels. Our findings thus elucidate a critical role for Plk1 in CyclinB1-Cdk1 activation and mitotic entry and outline how CyclinA2-Cdk, an S-promoting factor, poises cells for commitment to mitosis.