CP110, a cell cycle-dependent CDK substrate, regulates centrosome duplication in human cells
CP110, a cell cycle-dependent CDK substrate, regulates centrosome duplication in human cells
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DOI：
10.1016/s1534-5807(02)00258-7
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发表时间：
2002-09-01
影响因子：
11.8
通讯作者：
Dynlacht, BD
中科院分区：
文献类型：
--
作者：
Chen, ZH;Indjeian, VB;Dynlacht, BD
中心体的复制和分离与某些细胞周期事件密切相关，尤其是细胞周期蛋白依赖性蛋白激酶(CDK)的激活。然而，目前发现的推动这些事件的CDK目标相对较少。在这里，我们已经对CDK底物进行了筛选，并分离出了一个靶点CP110，它在体外和体内都被CDK磷酸化。人CP110定位于中心体。它的表达在G1-S相变时强烈诱导，与中心体复制的启动相一致。RNAi介导的CP110缺失表明该蛋白在中心体复制中起重要作用。CP110磷酸化的长期中断会导致非计划的中心体分离和显性多倍体。我们的数据表明，CP110是一个促进中心体复制的生理中心体CDK靶标，它的去调控可能导致基因组的不稳定。
Centrosome duplication and separation are linked inextricably to certain cell cycle events, in particular activation of cyclin-dependent kinases (CDKs). However, relatively few CDK targets driving these events have been uncovered. Here, we have performed a screen for CDK substrates and have isolated a target, CP110, which is phosphorylated by CDKs in vitro and in vivo. Human CP110 localizes to centrosomes. Its expression is strongly induced at the G1-to-S phase transition, coincident with the initiation of centrosome duplication. RNAi-mediated depletion of CP110 indicates that this protein plays an essential role in centrosome duplication. Long-term disruption of CP110 phosphorylation leads to unscheduled centrosome separation and overt polyploidy. Our data suggest that CP110 is a physiological centrosomal CDK target that promotes centrosome duplication, and its deregulation may contribute to genomic instability.