Ubiquitylation and proteasomal degradation of the p21Cip1, p27Kip1 and p57Kip2 CDK inhibitors

The expression levels of the p21 Cip1 family CDK inhibitors (CKIs), p21 Cip1 , p27 Kip1 and p57 Kip2 , play a pivotal role in the precise regulation of cyclin-dependent kinase (CDK) activity, which is instrumental to proper cell cycle progression. The stabilities of p21 Cip1 , p27 Kip1 and p57 Kip2 are all tightly and differentially regulated by ubiquitylation and proteasome-mediated degradation during various stages of the cell cycle, either in steady state or in response to extracellular stimuli, which often elicit site-specific phosphorylation of CKIs triggering their degradation.