Cell cycle regulation of central spindle assembly
Cell cycle regulation of central spindle assembly
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DOI：
10.1038/nature02767
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发表时间：
2004-08-19
期刊：
影响因子：
64.8
通讯作者：
Glotzer, M
中科院分区：
文献类型：
--
作者：
Mishima, M;Pavicic, V;Glotzer, M
在有丝分裂后期，双极纺锤体负责分离姐妹染色单体。微管马达蛋白产生纺锤体双极性，使纺锤体能够进行机械功（1）。纺锤体结构的一个主要变化发生在后期开始时，中央纺锤体组装开始。这种结构调节胞质分裂的起始，并对其完成至关重要（2）。中央纺锤体组装需要由秀丽隐杆线虫ZEN-4（哺乳动物直向同源物MKLP 1）驱动蛋白样蛋白和Rho家族GAP CYK-4（MgcRacGAP）组成的中央-纺锤体蛋白复合物。在这里，我们描述了一个调节机制，控制中央纺锤体组装的时间。有丝分裂激酶Cdk 1/细胞周期蛋白B磷酸化MKLP 1亚家族的碱性氨基末端延伸特征内的保守位点上的ZEN-4的马达结构域。Cdk 1的磷酸化通过降低ZEN-4对微管的亲和力来降低其运动活性。阻止ZEN-4/MKLP 1的Cdk 1磷酸化导致增强的中期纺锤体定位和染色体分离缺陷。因此，MKLP 1驱动蛋白的马达结构域的磷酸化调节确保了在细胞周期中的适当时间发生中心纺锤体组装并维持基因组稳定性。
The bipolar mitotic spindle is responsible for segregating sister chromatids at anaphase. Microtubule motor proteins generate spindle bipolarity and enable the spindle to perform mechanical work(1). A major change in spindle architecture occurs at anaphase onset when central spindle assembly begins. This structure regulates the initiation of cytokinesis and is essential for its completion(2). Central spindle assembly requires the central-spindlin complex composed of the Caenorhabditis elegans ZEN-4 (mammalian orthologue MKLP1) kinesin-like protein and the Rho family GAP CYK-4 (MgcRacGAP). Here we describe a regulatory mechanism that controls the timing of central spindle assembly. The mitotic kinase Cdk1/cyclin B phosphorylates the motor domain of ZEN-4 on a conserved site within a basic amino-terminal extension characteristic of the MKLP1 subfamily. Phosphorylation by Cdk1 diminishes the motor activity of ZEN-4 by reducing its affinity for microtubules. Preventing Cdk1 phosphorylation of ZEN-4/MKLP1 causes enhanced metaphase spindle localization and defects in chromosome segregation. Thus, phosphoregulation of the motor domain of MKLP1 kinesin ensures that central spindle assembly occurs at the appropriate time in the cell cycle and maintains genomic stability.