Rac1-dependent recruitment of PAK2 to G 2 phase centrosomes and their roles in the regulation of mitotic entry

TY - JOUR

T1 - Rac1-dependent recruitment of PAK2 to G 2 phase centrosomes and their roles in the regulation of mitotic entry

AU - May, Martin

AU - Schelle, Ilona

AU - Brakebusch, Cord Herbert

AU - Rottner, Klemens

AU - Genth, Harald

PY - 2014/7/15

Y1 - 2014/7/15

N2 - During mitotic entry, the centrosomes provide a scaffold for initial activation of the CyclinB/Cdk1 complex, the mitotic kinase Aurora A, and the Aurora A-activating kinase p21-activated kinase (PAK). The activation of PAK at the centrosomes is yet regarded to happen independently of the Rho-GTPases Rac/Cdc42. In this study, Rac1 (but not RhoA or Cdc42) is presented to associate with the centrosomes from early G 2 phase until prometaphase in a cell cycle-dependent fashion, as evidenced by western blot analysis of prepared centrosomes and by immunolabeling. PAK associates with the G 2/M-phase centrosomes in a Rac1-dependent fashion. Furthermore, specific inhibition of Rac1 by C. difficile toxinB-catalyzed glucosylation or by knockout results in inhibited activation of PAK1/2, Aurora A, and the CyclinB/Cdk1 complex in late G 2 phase/prophase and delayed mitotic entry. Inhibition of PAK activation at late G 2-phase centrosomes caused by Rac1 inactivation coincides with impeded activation of Aurora A and the CyclinB/Cdk1 complex and delayed mitotic entry.

AB - During mitotic entry, the centrosomes provide a scaffold for initial activation of the CyclinB/Cdk1 complex, the mitotic kinase Aurora A, and the Aurora A-activating kinase p21-activated kinase (PAK). The activation of PAK at the centrosomes is yet regarded to happen independently of the Rho-GTPases Rac/Cdc42. In this study, Rac1 (but not RhoA or Cdc42) is presented to associate with the centrosomes from early G 2 phase until prometaphase in a cell cycle-dependent fashion, as evidenced by western blot analysis of prepared centrosomes and by immunolabeling. PAK associates with the G 2/M-phase centrosomes in a Rac1-dependent fashion. Furthermore, specific inhibition of Rac1 by C. difficile toxinB-catalyzed glucosylation or by knockout results in inhibited activation of PAK1/2, Aurora A, and the CyclinB/Cdk1 complex in late G 2 phase/prophase and delayed mitotic entry. Inhibition of PAK activation at late G 2-phase centrosomes caused by Rac1 inactivation coincides with impeded activation of Aurora A and the CyclinB/Cdk1 complex and delayed mitotic entry.

U2 - 10.4161/cc.29279

DO - 10.4161/cc.29279

M3 - Journal article

C2 - 24840740

SN - 1538-4101

VL - 13

SP - 2211

EP - 2221

JO - Cell Cycle

JF - Cell Cycle

IS - 14

ER -