Department of Gynecology and Obstetrics, School of Medicine, J. W. Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Mol Cell Biol. 2010 Jun;30(11):2594-607. doi: 10.1128/MCB.00098-10. Epub 2010 Apr 5.
Mitotic centromere-associated kinesin (MCAK) plays an essential role in spindle formation and in correction of improper microtubule-kinetochore attachments. The localization and activity of MCAK at the centromere/kinetochore are controlled by Aurora B kinase. However, MCAK is also abundant in the cytosol and at centrosomes during mitosis, and its regulatory mechanism at these sites is unknown. We show here that cyclin-dependent kinase 1 (Cdk1) phosphorylates T537 in the core domain of MCAK and attenuates its microtubule-destabilizing activity in vitro and in vivo. Phosphorylation of MCAK by Cdk1 promotes the release of MCAK from centrosomes and is required for proper spindle formation. Interfering with the regulation of MCAK by Cdk1 causes dramatic defects in spindle formation and in chromosome positioning. This is the first study demonstrating that Cdk1 regulates the localization and activity of MCAK in mitosis by directly phosphorylating the catalytic core domain of MCAK.
有丝分裂着丝粒相关驱动蛋白（MCAK）在纺锤体形成和纠正错误的微管-动粒连接中起着重要作用。着丝粒/动粒处 MCAK 的定位和活性受 Aurora B 激酶的控制。然而，MCAK 在有丝分裂期间在细胞质和中心体中也很丰富，其在这些部位的调节机制尚不清楚。我们在这里表明，细胞周期蛋白依赖性激酶 1（Cdk1）磷酸化 MCAK 核心结构域中的 T537，并在体外和体内减弱其微管解聚活性。Cdk1 对 MCAK 的磷酸化促进 MCAK 从中心体释放，这对于正确的纺锤体形成是必需的。干扰 Cdk1 对 MCAK 的调节会导致纺锤体形成和染色体定位的严重缺陷。这是第一项研究，表明 Cdk1 通过直接磷酸化 MCAK 的催化核心结构域来调节有丝分裂中 MCAK 的定位和活性。
