rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
1999-12-8
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Microtubule-Associated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligodeoxyribonucleotides, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/S-Phase Kinase-Associated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitins
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1465-7392
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:volume |
1
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
193-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10559916-Base Sequence,
pubmed-meshheading:10559916-Cell Cycle Proteins,
pubmed-meshheading:10559916-Cell Line,
pubmed-meshheading:10559916-Cyclin-Dependent Kinase Inhibitor p27,
pubmed-meshheading:10559916-Cyclin-Dependent Kinases,
pubmed-meshheading:10559916-Enzyme Inhibitors,
pubmed-meshheading:10559916-HeLa Cells,
pubmed-meshheading:10559916-Humans,
pubmed-meshheading:10559916-Kinetics,
pubmed-meshheading:10559916-Microtubule-Associated Proteins,
pubmed-meshheading:10559916-Oligodeoxyribonucleotides, Antisense,
pubmed-meshheading:10559916-Phosphorylation,
pubmed-meshheading:10559916-Protein Binding,
pubmed-meshheading:10559916-RNA, Messenger,
pubmed-meshheading:10559916-S-Phase Kinase-Associated Proteins,
pubmed-meshheading:10559916-Tumor Suppressor Proteins,
pubmed-meshheading:10559916-Ubiquitins
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pubmed:year |
1999
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pubmed:articleTitle |
SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27.
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pubmed:affiliation |
Department of Pathology, New York University Medical Center, New York 10016, USA.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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