RhoA and RhoC are both required for the ROCK II-dependent promotion of centrosome duplication.
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.
Kanai
M
M
Molecular Oncology Program, H Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Crowe
M S
MS
Zheng
Y
Y
Vande Woude
G F
GF
Fukasawa
K
K
D000818:Animals; D018385:Centrosome / Q000502:physiology*; D051379:Mice; D041681:NIH 3T3 Cells; D015854:Up-Regulation; D018631:ras Proteins / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein; D020743:rhoB GTP-Binding Protein / Q000378:metabolism; D000075024:rhoC GTP-Binding Protein
D054460:rho-Associated Kinases; C526380:RhoA protein, mouse; C512911:Rhoc protein, mouse; D018631:ras Proteins; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D020743:rhoB GTP-Binding Protein; D000075024:rhoC GTP-Binding Protein