Rac1-dependent recruitment of PAK2 to G₂phase centrosomes and their roles in the regulation of mitotic entry

Large clostridial glycosylating toxins modifying small GTPases

“…Treatment of proliferating cells with either LCGT further results in inhibited cell cycle progression at the G1-S, as well as the G2-M boundaries [62,64,91,92]. Rac1 glucosylation suppresses cyclin D expression and delays cyclin B activation, resulting in G1-S arrest and delayed G2-M transition, respectively (Figure 16.6) [64,93,94].…”

“…Rac1 glucosylation suppresses cyclin D expression and delays cyclin B activation, resulting in G1-S arrest and delayed G2-M transition, respectively (Figure 16.6) [64,93,94]. In cells treated with RhoA-glucosylating LCGTs such as TcdA and TcdB, RhoAdependent contractile ring formation in cytokinesis is blocked.…”

“…Furthermore, Rho-GTPases regulate the CKIs p21(Cip1/Waf1) and p27(Kip1). In mitotic entry (G2-M transition), Rac1 activates the CyclinB/Cdk1 complex by a pathway involving p21-activated kinases (PAKs) and the mitotic kinases AuroraA and Polo-like kinase 1 (Plk1)[62][63][64]. Finally, RhoA plays a key role in actin reorganization in mitosis, including the regulation of mitotic cell rounding and contractile ring formation (for a review, see[65])(Figure 16.6).…”

Mitotic entry elucidated with bacterial toxin toolbox

“…Treatment of synchronized HeLa cells in G 2 phase of the cell cycle with this specific Rac-inhibiting toxin prevented the activation of PAK, Aurora A, and Cdk1/cyclinB at the G 2 /M border and delayed entry of cells into mitosis for 2 h. This observation indicates Rac—but not Cdc42 or Rho—as the missing player in this process 7 . Where is Rac’s mitotic point of entry?…”

“…Published in this volume of Cell Cycle , May and coworkers tackled this question by extending the work by Ando et al In cleverly designed experiments they used a variant of Clostridium difficile toxin B that selectively inhibits Rac activity in living cells 7 . Treatment of synchronized HeLa cells in G 2 phase of the cell cycle with this specific Rac-inhibiting toxin prevented the activation of PAK, Aurora A, and Cdk1/cyclinB at the G 2 /M border and delayed entry of cells into mitosis for 2 h. This observation indicates Rac—but not Cdc42 or Rho—as the missing player in this process 7 .…”