APC/C(Cdc20) controls the ubiquitin-mediated degradation of p21 in prometaphase.

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/C(Cdc20)-mediated ubiquitylation of p21. Overexpression of Cdc20 or Skp2 destabilized wild-type 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/C(Cdc20)-mediated degradation of p21 contributes to the full activation of Cdk1 necessary for mitotic events and prevents mitotic slippage during spindle checkpoint activation.
Mesh Terms:
Animals, CDC2 Protein Kinase, Cell Cycle Proteins, Colonic Neoplasms, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinase Inhibitor p27, Enzyme Inhibitors, Fibroblasts, Glioblastoma, Humans, Immunoblotting, Immunoprecipitation, Lung, Mice, Mice, Knockout, Mutagenesis, Site-Directed, Prometaphase, S-Phase Kinase-Associated Proteins, Ubiquitin, Ubiquitin-Protein Ligase Complexes, Ubiquitin-Protein Ligases
Mol. Cell
Date: Aug. 03, 2007
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