Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1999-12-8
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1465-7392
pubmed:author
pubmed:issnType
Print
pubmed:volume
1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
193-9
pubmed:dateRevised
2009-11-19
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
pubmed:year
1999
pubmed:articleTitle
SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27.
pubmed:affiliation
Department of Pathology, New York University Medical Center, New York 10016, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't