Skp2 is required for the ubiquitin-mediated
degradation of the Cdk-inhibitor p27
Carrano AC, Eytan E, Hershko A, Pagano M
Nature Cell Biol 1999; 1: 193-199
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 degradation
of p27 depend upon its phosphorylation by cyclin/Cdk complexes. However,
the ubiquitin ligase necessary for p27 ubiquitination has not been identified.
Here we demonstrate that the F-box protein Skp2 specifically recognizes
p27 in a phosphorylation-dependent manner which 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.
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"News & Views" (Nature Cell Biol 1999)