期刊
ONCOGENE
卷 29, 期 45, 页码 6040-6050出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2010.328
关键词
centrosome; Rho; ROCK II; CDK2; cyclin E; NPM/B23
资金
- National Institute of Health [CA90522]
- James & Esther King Biomedical Research Program [09KN-05-23139]
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 superactivation 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 overactivation of RhoA, as well as RhoC, but not RhoB, promoted centrosome duplication and centrosome amplification. Oncogene (2010) 29, 6040 6050; doi:10.1038/onc.2010.328; published online 9 August 2010
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