Rac1-dependent recruitment of PAK2 to G 2 phase centrosomes and their roles in the regulation of mitotic entry
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Rac1-dependent recruitment of PAK2 to G 2 phase centrosomes and their roles in the regulation of mitotic entry. / May, Martin; Schelle, Ilona; Brakebusch, Cord Herbert; Rottner, Klemens; Genth, Harald.
In: Cell Cycle, Vol. 13, No. 14, 19.05.2014, p. 2211-21.Research output: Contribution to journal › Journal article › Research › peer-review
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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 - 2014/5/19
Y1 - 2014/5/19
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
VL - 13
SP - 2211
EP - 2221
JO - Cell Cycle
JF - Cell Cycle
SN - 1538-4101
IS - 14
ER -
ID: 112840657