Cyclin-dependent kinase control of centrosome duplication
Cyclin-dependent kinase control of centrosome duplication
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DOI：
10.1073/pnas.96.6.2817
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发表时间：
1999-03-16
影响因子：
11.1
通讯作者：
Stearns, T
中科院分区：
文献类型：
--
作者：
Lacey, KR;Jackson, PK;Stearns, T
中心体使微管成核并在每个细胞周期复制一次。这种复制和随后的有丝分裂分离导致一个中心体/细胞比率的维持。中心体复制发生在体细胞的G（1）/S转换期间，并且必须与核细胞周期的事件偶联;未能协调复制和有丝分裂导致中心体数量异常和异常有丝分裂。使用在体内和体外试验，我们表明，在非洲爪蟾胚胎中心体复制需要细胞周期蛋白/cdk 2激酶活性。将cdk（细胞周期蛋白依赖性激酶）抑制剂p21注射到分裂胚胎的一个卵裂球中，可以阻断该卵裂球中的中心体复制;相关的cdk抑制剂p27也有类似的效果。使用非洲爪蟾提取物的体外系统进行中心体内配对中心粒的分离。这种中心粒分离活性依赖于细胞周期蛋白/cdk 2活性; cdk 2或两种活化细胞周期蛋白（细胞周期蛋白A和细胞周期蛋白E）的耗竭消除了中心粒分离活性。此外，中心粒分离被有丝分裂状态抑制，表明细胞周期与中心体的周期性复制有关。
Centrosomes nucleate microtubules and duplicate once per cell cycle. This duplication and subsequent segregation in mitosis results in maintenance of the one centrosome/cell ratio. Centrosome duplication occurs during the G(1)/S transition in somatic cells and must be coupled to the events of the nuclear cell cycle; failure to coordinate duplication and mitosis results in abnormal numbers of centrosomes and aberrant mitoses. Using both in vivo and in vitro assays, we show that centrosome duplication in Xenopus laevis embryos requires cyclin/cdk2 kinase activity. Injection of the cdk (cyclin-dependent kinase) inhibitor p21 into one blastomere of a dividing embryo blocks centrosome duplication in that blastomere; the related cdk inhibitor p27 has a similar effect. An in vitro system using Xenopus extracts carries out separation of the paired centrioles within the centrosome. This centriole separation activity is dependent on cyclin/cdk2 activity; depletion of either cdk2 or of the two activating cyclins, cyclin A and cyclin E, eliminates centriole separation activity. In addition, centriole separation is inhibited by the mitotic state, suggesting a mechanism of linking the cell cycle to periodic duplication of the centrosome.