Polo-like kinase 1 triggers the initiation of cytokinesis in human cells by promoting recruitment of the RhoGEF Ect2 to the central spindle
Polo-like kinase 1 triggers the initiation of cytokinesis in human cells by promoting recruitment of the RhoGEF Ect2 to the central spindle
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DOI：
10.1016/j.devcel.2007.03.013
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发表时间：
2007-05-01
影响因子：
11.8
通讯作者：
Peters, Jan-Michael
中科院分区：
文献类型：
--
作者：
Petronczki, Mark;Glotzer, Michael;Peters, Jan-Michael
动物细胞的胞质分裂需要以肌动球蛋白为基础的收缩环进入分离的姐妹基因组之间。定位的RhoGEF Ect2的中央纺锤体在后期促进局部激活的RhoA GTdR，诱导组装和收缩环的侵入。在这里，我们已经使用BI 2536，有丝分裂激酶PIK1的抑制剂，以分析这种酶在人类细胞有丝分裂晚期的功能。我们发现，PIK1的行为后，Cdk1失活和独立的极光B，以促进RhoA积累在赤道，收缩环的形成，和分裂沟的侵入。PIK1的抑制消除了Ect 2与其激活剂和中间区锚HsCyk 4的相互作用，从而防止Ect 2定位于中央纺锤体。我们认为，晚期有丝分裂PIK1活性促进招募Ect2的中央纺锤体，触发胞质分裂的启动，并有助于在人类细胞的卵裂平面规范。
Cytokinesis of animal cells requires ingression of the actomyosin-based contractile ring between segregated sister genomes. Localization of the RhoGEF Ect2 to the central spindle at anaphase promotes local activation of the RhoA GTPase, which induces assembly and ingression of the contractile ring. Here we have used BI 2536, an inhibitor of the mitotic kinase PIk1, to analyze the functions of this enzyme during late mitosis in human cells. We show that PIk1 acts after Cdk1 inactivation and independently from Aurora B to promote RhoA accumulation at the equator, contractile ring formation, and cleavage furrow ingression. Inhibition of PIk1 abolishes the interaction of Ect2 with its activator and midzone anchor, HsCyk4, thereby preventing localization of Ect2 to the central spindle. We propose that late mitotic PIk1 activity promotes recruitment of Ect2 to the central spindle, triggering the initiation of cytokinesis and contributing to cleavage plane specification in human cells.