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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
1999-4-13
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pubmed:abstractText |
Destruction of the transcriptional inhibitor IkappaB by the ubiquitin (Ub) system is required for signal-dependent activation of the multifunctional transcriptional factor NF-kappaB, but details of this ubiquitination are largely unknown. We report here that the IkappaBalpha-ubiquitin ligase (IkappaBalpha-E3) is an SCF-like complex containing Skp1, cullin-1, and two homologous F-box/WD40-repeat proteins, betaTrCP1 and betaTrCP2. Intriguingly, all these components are cooperatively recruited to bind to a phosphorylated IkappaBalpha (pIkappaBalpha) produced by tumor necrosis factor-alpha (TNF-alpha) stimulation. IkappaBalpha-E3 bound to pIkappaBalpha catalyzed in vitro ubiquitination of pIkappaBalpha in the presence of ATP, Ub, and E1-activating and E2-conjugating enzymes. Forced expression of betaTrCP1 and betaTrCP2 resulted in dramatic augmentation of the in vitro polyubiquitination activity of IkappaBalpha-E3. These results indicate that the long-sought IkappaBalpha-E3 is an SCF-like complex consisting of multiple proteins which are coordinately assembled during phosphorylation of IkappaBalpha in response to external signals.
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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/BTRC protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cullin 1,
http://linkedlifedata.com/resource/pubmed/chemical/Cullin Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/FBXW11 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappaB inhibitor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/S-Phase Kinase-Associated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitins,
http://linkedlifedata.com/resource/pubmed/chemical/beta-Transducin Repeat-Containing...
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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 1999 Academic Press.
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pubmed:issnType |
Print
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pubmed:day |
5
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pubmed:volume |
256
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
127-32
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pubmed:dateRevised |
2007-5-16
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pubmed:meshHeading |
pubmed-meshheading:10066435-Amino Acid Sequence,
pubmed-meshheading:10066435-Cell Cycle Proteins,
pubmed-meshheading:10066435-Cullin Proteins,
pubmed-meshheading:10066435-DNA-Binding Proteins,
pubmed-meshheading:10066435-GTP-Binding Proteins,
pubmed-meshheading:10066435-Gene Library,
pubmed-meshheading:10066435-HeLa Cells,
pubmed-meshheading:10066435-Humans,
pubmed-meshheading:10066435-I-kappa B Proteins,
pubmed-meshheading:10066435-Ligases,
pubmed-meshheading:10066435-Molecular Sequence Data,
pubmed-meshheading:10066435-Multienzyme Complexes,
pubmed-meshheading:10066435-Phosphorylation,
pubmed-meshheading:10066435-Precipitin Tests,
pubmed-meshheading:10066435-Protein Binding,
pubmed-meshheading:10066435-S-Phase Kinase-Associated Proteins,
pubmed-meshheading:10066435-Sequence Homology, Amino Acid,
pubmed-meshheading:10066435-Signal Transduction,
pubmed-meshheading:10066435-Transfection,
pubmed-meshheading:10066435-Tumor Necrosis Factor-alpha,
pubmed-meshheading:10066435-Ubiquitin-Protein Ligases,
pubmed-meshheading:10066435-Ubiquitins,
pubmed-meshheading:10066435-beta-Transducin Repeat-Containing Proteins
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pubmed:year |
1999
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pubmed:articleTitle |
IkappaBalpha ubiquitination is catalyzed by an SCF-like complex containing Skp1, cullin-1, and two F-box/WD40-repeat proteins, betaTrCP1 and betaTrCP2.
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pubmed:affiliation |
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Ibaraki, Tsukuba-shi, 305-8585, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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