Okuda M, Horn H F, Tarapore P, Tokuyama Y, Smulian A G, Chan P K, Knudsen E S, Hofmann I A, Snyder J D, Bove K E, Fukasawa K
Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Ohio 45267, USA.
Cell. 2000 Sep 29;103(1):127-40. doi: 10.1016/s0092-8674(00)00093-3.
In animal cells, duplication of centrosomes and DNA is coordinated. Since CDK2/cyclin E triggers initiation of both events, activation of CDK2/cyclin E is thought to link these two events. We identified nucleophosmin (NPM/B23) as a substrate of CDK2/cyclin E in centrosome duplication. NPM/B23 associates specifically with unduplicated centrosomes, and NPM/B23 dissociates from centrosomes by CDK2/cyclin E-mediated phosphorylation. An anti-NPM/B23 antibody, which blocks this phosphorylation, suppresses the initiation of centrosome duplication in vivo. Moreover, expression of a nonphosphorylatable mutant NPM/ B23 in cells effectively blocks centrosome duplication. Thus, NPM/B23 is a target of CDK2/cyclin E in the initiation of centrosome duplication.
在动物细胞中，中心体的复制与DNA的复制是协调进行的。由于CDK2/细胞周期蛋白E触发了这两个事件的起始，因此CDK2/细胞周期蛋白E的激活被认为将这两个事件联系了起来。我们鉴定出核磷蛋白（NPM/B23）是中心体复制过程中CDK2/细胞周期蛋白E的一个底物。NPM/B23特异性地与未复制的中心体结合，并且NPM/B23通过CDK2/细胞周期蛋白E介导的磷酸化作用从中心体上解离。一种能阻断这种磷酸化作用的抗NPM/B23抗体在体内可抑制中心体复制的起始。此外，细胞中不可磷酸化的突变型NPM/B23的表达有效地阻断了中心体的复制。因此，NPM/B23是中心体复制起始过程中CDK2/细胞周期蛋白E的一个作用靶点。
