Cdk phosphorylation licenses Kif4A chromosome localization required for early mitotic progression
Cdk phosphorylation licenses Kif4A chromosome localization required for early mitotic progression
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Cdk 磷酸化许可早期有丝分裂进展所需的 Kif4A 染色体定位
DOI：
10.1093/jmcb/mjy033
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发表时间：
2018-08-01
影响因子：
5.5
通讯作者：
Jiang, Wei
中科院分区：
文献类型：
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作者：
Dong, Zhixiong;Zhu, Changjun;Jiang, Wei
染色体驱动蛋白Kif 4A控制适当的染色体凝聚、聚集/排列和胞质分裂，以确保忠实的遗传。在这里，我们报告说，Cdk磷酸化的人Kif 4A在T1161许可Kif 4A染色体定位，这反过来又控制Kif 4A早期有丝分裂功能。磷酸化Kif 4A（Kif 4AWT）或Cdk磷酸模拟Kif 4A突变体（Kif 4ATE）与染色体和凝聚素I（非SMC亚基CAP-G和核心亚基SMC 2）相关，以调节早期有丝分裂中的染色体凝聚、纺锤体形态和染色体聚集/排列。相反，Cdk非磷酸化Kif 4A突变体（Kif 4ATA）既不能定位于染色体上，也不能与CAP-G和SMC 2结合。此外，Kif 4ATA不能挽救缺陷的染色体凝聚，纺锤体形态，或染色体congression/对齐的细胞内源性Kif 4A，激活有丝分裂检查点和延迟早期有丝分裂进程耗尽。然而，通过将Kif 4ATA与组蛋白H1融合将Kif 4ATA靶向染色体导致Kif 4A的染色体和纺锤体功能在内源性Kif 4A耗尽的细胞中恢复，类似于Kif 4AWT和Kif 4ATE。因此，我们的研究结果表明，Cdk磷酸化许可的染色体定位的Kif 4A起着至关重要的作用，在调节早期有丝分裂功能的Kif 4A是重要的早期有丝分裂进程。
The chromokinesin Kif4A controls proper chromosome condensation, congression/alignment, and cytokinesis to ensure faithful genetic inheritance. Here, we report that Cdk phosphorylation of human Kif4A at T1161 licenses Kif4A chromosomal localization, which, in turn, controls Kif4A early mitotic function. Phosphorylated Kif4A (Kif4AWT) or Cdk phospho-mimetic Kif4A mutant (Kif4ATE) associated with chromosomes and condensin I (non-SMC subunit CAP-G and core subunit SMC2) to regulate chromosome condensation, spindle morphology, and chromosome congression/alignment in early mitosis. In contrast, Cdk non-phosphorylatable Kif4A mutant (Kif4ATA) could neither localize on chromosomes nor associate with CAP-G and SMC2. Furthermore, Kif4ATA could not rescue defective chromosome condensation, spindle morphology, or chromosome congression/alignment in cells depleted of endogenous Kif4A, which activated a mitotic checkpoint and delayed early mitotic progression. However, targeting Kif4ATA to chromosomes by fusion of Kif4ATA with Histone H1 resulted in restoration of chromosome and spindle functions of Kif4A, similar to Kif4AWT and Kif4ATE, in cells depleted of endogenous Kif4A. Thus, our results demonstrate that Cdk phosphorylation-licensed chromosomal localization of Kif4A plays a critical role in regulating early mitotic functions of Kif4A that are important for early mitotic progression.