RhoA and RhoC are both required for the ROCK II-dependent promotion of centrosome duplication.
RhoA and RhoC are both required for the ROCK II-dependent promotion of centrosome duplication.
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DOI：
10.1038/onc.2010.328
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发表时间：
2010-11-11
期刊：
影响因子：
8
通讯作者：
Fukasawa, K.
中科院分区：
文献类型：
--
作者：
Kanai, M.;Crowe, M. S.;Zheng, Y.;Vande Woude, G. F.;Fukasawa, K.
CDK2-Cyclin E触发中心体复制，核磷蛋白(NPM/B23)被发现是其靶标之一。由CDK2-Cyclin E磷酸化的NPM/B23与Rho相关蛋白(ROCK II)具有较高的亲和力，并与ROCK II发生物理结合。NPM/B23与ROCK II的结合导致ROCK II的超激活，这是启动中心体复制的关键事件。ROCK II的激活还需要Rho小GTP酶与自身抑制区的结合；因此，活性Rho蛋白的可用性是中心体定位的ROCK II正确启动中心体复制的一个重要方面。Rho有三种亚型(RhoA、B和C)，它们都能够与ROCK II结合并启动ROCK II的激活。在这里，我们从中心体复制的启动方面研究了哪种Rho亚型(S)参与了ROCK II的激活。我们发现，中心体复制的启动需要RhoA和RhoC，而不是RhoB；过度激活RhoA和RhoC，但不需要RhoB，促进了中心体复制和中心体扩增。
CDK2-cyclin E triggers centrosome duplication, and nucleophosmin (NPM/B23) is found to be one of its targets. NPM/B23 phosphorylated by CDK2-cyclin E acquires a high binding affinity to Rho-associated kinase (ROCK II), and physically associates with ROCK II. The NPM/B23-binding results in super-activation of ROCK II, which is a critical event for initiation of centrosome duplication. The activation of ROCK II also requires the binding of Rho small GTPase to the auto-inhibitory region; hence the availability of the active Rho protein is an important aspect of the centrosomally localized ROCK II to properly initiate centrosome duplication. There are three isoforms of Rho (RhoA, B, and C), all of which are capable of binding to and priming the activation of ROCK II. Here, we investigated which Rho isoform(s) are involved in the activation of ROCK II in respect to the initiation of centrosome duplication. We found that both RhoA and RhoC, but not RhoB, were required for initiation of centrosome duplication, and over-activation of RhoA as well as RhoC, but not RhoB, promoted centrosome duplication and centrosome amplification.
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作者：
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