Format

Send to

Choose Destination
Oncogene. 2010 Nov 11;29(45):6040-50. doi: 10.1038/onc.2010.328. Epub 2010 Aug 9.

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

Author information

1
Molecular Oncology Program, H Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.

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.

PMID:
20697357
PMCID:
PMC2978787
DOI:
10.1038/onc.2010.328
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center