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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2001-3-12
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pubmed:abstractText |
Cyclin E is required for S phase entry. The subsequent ubiquitin-dependent degradation of cyclin E contributes to an orderly progression of the S phase. It has been shown that phosphorylation of threonine 380 (Thr380) in cyclin E provides a signal for its ubiquitin-dependent proteolysis. We report that SKP2, an F-box protein and a substrate-targeting component of the SCF(SKP2) ubiquitin E3 ligase complex, mediates cyclin E degradation. In vitro, SKP2 specifically interacted with the cyclin E peptide containing the phosphorylated-Thr380 but not with a cognate nonphosphorylated peptide. In vivo, expression of SKP2 induced cyclin E polyubiquitination and degradation. Conversion of Thr380 into nonphosphorylatable amino acids caused significant resistance of cyclin E to SKP2. The presence of the CDK inhibitor p27(Kip1) also prevented the SKP2-dependent degradation of cyclin E. Our findings suggest that SKP2 regulates cyclin E stability, thus contributing to the control of S phase progression.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0006-291X
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2001 Academic Press.
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pubmed:issnType |
Print
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pubmed:day |
9
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pubmed:volume |
281
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
884-90
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:11237742-Amino Acid Sequence,
pubmed-meshheading:11237742-Amino Acid Substitution,
pubmed-meshheading:11237742-Animals,
pubmed-meshheading:11237742-Cell Cycle Proteins,
pubmed-meshheading:11237742-Cell Line,
pubmed-meshheading:11237742-Cyclin E,
pubmed-meshheading:11237742-Cyclin-Dependent Kinase Inhibitor p27,
pubmed-meshheading:11237742-DNA, Recombinant,
pubmed-meshheading:11237742-Fibroblasts,
pubmed-meshheading:11237742-HeLa Cells,
pubmed-meshheading:11237742-Humans,
pubmed-meshheading:11237742-Microtubule-Associated Proteins,
pubmed-meshheading:11237742-Molecular Sequence Data,
pubmed-meshheading:11237742-Mutation,
pubmed-meshheading:11237742-Phosphorylation,
pubmed-meshheading:11237742-Protein Binding,
pubmed-meshheading:11237742-S-Phase Kinase-Associated Proteins,
pubmed-meshheading:11237742-Threonine,
pubmed-meshheading:11237742-Transfection,
pubmed-meshheading:11237742-Tumor Suppressor Proteins,
pubmed-meshheading:11237742-Ubiquitins
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pubmed:year |
2001
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pubmed:articleTitle |
The F-box protein SKP2 binds to the phosphorylated threonine 380 in cyclin E and regulates ubiquitin-dependent degradation of cyclin E.
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pubmed:affiliation |
Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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