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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2004-12-1
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pubmed:databankReference |
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pubmed:abstractText |
The cyclin-dependent kinase inhibitor p27(Kip1) is degraded at the G0-G1 transition of the cell cycle by the ubiquitin-proteasome pathway. Although the nuclear ubiquitin ligase (E3) SCF(Skp2) is implicated in p27(Kip1) degradation, proteolysis of p27(Kip1) at the G0-G1 transition proceeds normally in Skp2(-/-) cells. Moreover, p27(Kip1) is exported from the nucleus to the cytoplasm at G0-G1 (refs 9-11). These data suggest the existence of a Skp2-independent pathway for the degradation of p27(Kip1) at G1 phase. We now describe a previously unidentified E3 complex: KPC (Kip1 ubiquitination-promoting complex), consisting of KPC1 and KPC2. KPC1 contains a RING-finger domain, and KPC2 contains a ubiquitin-like domain and two ubiquitin-associated domains. KPC interacts with and ubiquitinates p27(Kip1) and is localized to the cytoplasm. Overexpression of KPC promoted the degradation of p27(Kip1), whereas a dominant-negative mutant of KPC1 delayed p27(Kip1) degradation. The nuclear export of p27(Kip1) by CRM1 seems to be necessary for KPC-mediated proteolysis. Depletion of KPC1 by RNA interference also inhibited p27(Kip1) degradation. KPC thus probably controls degradation of p27(Kip1) in G1 phase after export of the latter from the nucleus.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Cdkn1b protein, mouse,
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/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Karyopherins,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Subunits,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/exportin 1 protein
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1465-7392
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
6
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1229-35
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15531880-Active Transport, Cell Nucleus,
pubmed-meshheading:15531880-Amino Acid Sequence,
pubmed-meshheading:15531880-Animals,
pubmed-meshheading:15531880-Base Sequence,
pubmed-meshheading:15531880-Cell Cycle Proteins,
pubmed-meshheading:15531880-Cyclin-Dependent Kinase Inhibitor p27,
pubmed-meshheading:15531880-Cytoplasm,
pubmed-meshheading:15531880-DNA, Complementary,
pubmed-meshheading:15531880-Down-Regulation,
pubmed-meshheading:15531880-G1 Phase,
pubmed-meshheading:15531880-Humans,
pubmed-meshheading:15531880-Karyopherins,
pubmed-meshheading:15531880-Macromolecular Substances,
pubmed-meshheading:15531880-Mice,
pubmed-meshheading:15531880-Molecular Sequence Data,
pubmed-meshheading:15531880-Mutation,
pubmed-meshheading:15531880-NIH 3T3 Cells,
pubmed-meshheading:15531880-Peptide Hydrolases,
pubmed-meshheading:15531880-Protein Structure, Tertiary,
pubmed-meshheading:15531880-Protein Subunits,
pubmed-meshheading:15531880-RNA Interference,
pubmed-meshheading:15531880-Rabbits,
pubmed-meshheading:15531880-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:15531880-Tumor Suppressor Proteins,
pubmed-meshheading:15531880-Ubiquitin,
pubmed-meshheading:15531880-Ubiquitin-Protein Ligases
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pubmed:year |
2004
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pubmed:articleTitle |
Cytoplasmic ubiquitin ligase KPC regulates proteolysis of p27(Kip1) at G1 phase.
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pubmed:affiliation |
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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