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RhoA and RhoC are both required for the ROCK II-dependent promotion of centrosome duplication

Oncogene volume 29, pages 6040–6050 (2010)Cite this article

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Abstract

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.

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Acknowledgements

We thank M Rowland and B Nepon-Sixt for technical assistance and core staff at the analytical microscopy core facility and molecular biology core facility in H Lee Moffitt Cancer Center. We also thank Dr Sebti for providing RhoB cDNA. This study is supported by the National Institute of Health (CA90522 to KF) and James & Esther King Biomedical Research Program (09KN-05–23139 to MK).

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Authors and Affiliations

  1. Molecular Oncology Program, H Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA

    M Kanai, M S Crowe & K Fukasawa

  2. Division of Experimental Hematology and Molecular Developmental Biology Program, Children's Hospital Research Foundation, University of Cincinnati, Cincinnati, OH, USA

    Y Zheng

  3. Van Andel Research Institute, Grand Rapids, MI, USA

    G F Vande Woude

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  1. M Kanai
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  2. M S Crowe
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  4. G F Vande Woude
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Correspondence to K Fukasawa.

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Kanai, M., Crowe, M., Zheng, Y. et al. RhoA and RhoC are both required for the ROCK II-dependent promotion of centrosome duplication. Oncogene 29, 6040–6050 (2010). https://doi.org/10.1038/onc.2010.328

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