SKP2 is required for ubiquitin- mediated degradation of the CDK inhibitor p27.
Degradation of the mammalian cyclin-dependent kinase (CDK) inhibitor p27 is required for the cellular transition from quiescence to the proliferative state. The ubiquitination and subsequent degradation of p27 depend on its phosphorylation by cyclin-CDK complexes. However, the ubiquitin-protein ligase necessary for p27 ubiquitination has not been identified. Here we show that the F-box protein SKP2 specifically recognizes p27 in a phosphorylation-dependent manner that is characteristic of an F-box-protein-substrate interaction. Furthermore, both in vivo and in vitro, SKP2 is a rate-limiting component of the machinery that ubiquitinates and degrades phosphorylated p27. Thus, p27 degradation is subject to dual control by the accumulation of both SKP2 and cyclins following mitogenic stimulation.[1]References
- SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27. Carrano, A.C., Eytan, E., Hershko, A., Pagano, M. Nat. Cell Biol. (1999) [Pubmed]
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