APC/CCdc20 Controls the Ubiquitin-Mediated Degradation of p21 in Prometaphase
Virginia Amador, Sheng Ge, Patricia G. Santamarı´a, Daniele Guardavaccaro, and Michele Pagano

Mol Cell, 27, 462–473, 2007

During the G1/S transition, p21 proteolysis is mediated by Skp2; however, p21 reaccumulates
in G2 and is degraded again in prometaphase. How p21 degradation is controlled in mitosis remains unexplored. We found that Cdc20 (an activator of the ubiquitin ligase APC/C) binds p21 in cultured cells and identified a D box motif in p21 necessary for APC/CCdc20-mediated ubiquitylation of p21. Overexpression of Cdc20 or Skp2 destabilized wildtype p21; however, only Skp2, but not Cdc20, was able to destabilize a p21(D box) mutant. Silencing of Cdc20 induced an accumulation of p21, increased the fraction of p21 bound to Cdk1, and inhibited Cdk1 activity in p21+/+ prometaphase cells, but not in p21 / cells. Thus, in prometaphase Cdc20 positively regulates Cdk1 by mediating the degradation of p21. We propose that the APC/CCdc20-mediated degradation of p21 contributes to the full activation of Cdk1 necessary for mitotic events and prevents mitotic slippage during spindle checkpoint activation.


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