Complex formation of Plk1 and INCENP required for metaphase-anaphase transition
Complex formation of Plk1 and INCENP required for metaphase-anaphase transition
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DOI：
10.1038/ncb1350
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发表时间：
2006-02-01
影响因子：
21.3
通讯作者：
Inagaki, M
中科院分区：
文献类型：
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作者：
Goto, H;Kiyono, T;Inagaki, M
有丝分裂染色体动力学受许多有丝分裂激酶的协调活性调节（1），如细胞周期蛋白依赖性激酶1（Cdk 1）（2，3）、Aurora-B-4或Polo样激酶1（Plk 1）（5），但其协调机制仍不清楚。在这里，我们报道了Cdk 1磷酸化内着丝粒蛋白（INCENP）上的Thr 59和Thr 388，这调节了Aurora-B从前期到中期的定位（4）和激酶活性（6-8）。INCENP缺失破坏Plk 1定位，特别是在动粒。该表型通过INCENP野生型和在Thr 59突变为Ala（T59 A）而不是在Thr 388突变为Ala（T388 A）的INCENP的外源表达来挽救。用T388 A替换内源性INCENP导致从中期到后期的进展延迟。我们建议，INCENP磷酸化的Cdk 1是必要的招聘Plk 1的动粒，和复杂的形成Plk 1和Aurora-B INCENP可能发挥至关重要的作用，在调节染色体动力学。
Mitotic chromosomal dynamics is regulated by the coordinated activities of many mitotic kinases(1), such as cyclin-dependent kinase 1 (Cdk1)(2,3), Aurora-B-4 or Polo-like kinase 1 (Plk1)(5), but the mechanisms of their coordination remain unknown. Here, we report that Cdk1 phosphorylates Thr 59 and Thr 388 on inner centromere protein (INCENP), which regulates the localization(4) and kinase activity(6-8) of Aurora-B from prophase to metaphase. INCENP depletion disrupts Plk1 localization specifically at the kinetochore. This phenotype is rescued by the exogenous expression of INCENP wild type and INCENP mutated at Thr 59 to Ala (T59A), but not at Thr 388 to Ala (T388A). The replacement of endogenous INCENP with T388A resulted in the delay of progression from metaphase to anaphase. We propose that INCENP phosphorylation by Cdk1 is necessary for the recruitment of Plk1 to the kinetochore, and that the complex formation of Plk1 and Aurora-B on INCENP may play crucial roles in the regulation of chromosomal dynamics.