rdf:type |
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lifeskim:mentions |
umls-concept:C0026741,
umls-concept:C0084133,
umls-concept:C0084913,
umls-concept:C0337112,
umls-concept:C0530129,
umls-concept:C1166825,
umls-concept:C1336666,
umls-concept:C1524075,
umls-concept:C1546857,
umls-concept:C1710548,
umls-concept:C1879547
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pubmed:issue |
2
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pubmed:dateCreated |
2000-11-15
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pubmed:databankReference |
|
pubmed:abstractText |
TRAF6 is a signal transducer in the NF-kappaB pathway that activates IkappaB kinase (IKK) in response to proinflammatory cytokines. We have purified a heterodimeric protein complex that links TRAF6 to IKK activation. Peptide mass fingerprinting analysis reveals that this complex is composed of the ubiquitin conjugating enzyme Ubc13 and the Ubc-like protein Uev1A. We find that TRAF6, a RING domain protein, functions together with Ubc13/Uev1A to catalyze the synthesis of unique polyubiquitin chains linked through lysine-63 (K63) of ubiquitin. Blockade of this polyubiquitin chain synthesis, but not inhibition of the proteasome, prevents the activation of IKK by TRAF6. These results unveil a new regulatory function for ubiquitin, in which IKK is activated through the assembly of K63-linked polyubiquitin chains.
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pubmed:grant |
|
pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Biopolymers,
http://linkedlifedata.com/resource/pubmed/chemical/CHUK protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/IKBKB protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/IKBKE protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/Polyubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TNF Receptor-Associated Factor 6,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/UBE2V1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Conjugating Enzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitins
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0092-8674
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:day |
13
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pubmed:volume |
103
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pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
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pubmed:pagination |
351-61
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11057907-Amino Acid Sequence,
pubmed-meshheading:11057907-Biopolymers,
pubmed-meshheading:11057907-Cell-Free System,
pubmed-meshheading:11057907-Cloning, Molecular,
pubmed-meshheading:11057907-Dimerization,
pubmed-meshheading:11057907-Enzyme Activation,
pubmed-meshheading:11057907-HeLa Cells,
pubmed-meshheading:11057907-Humans,
pubmed-meshheading:11057907-I-kappa B Kinase,
pubmed-meshheading:11057907-Ligases,
pubmed-meshheading:11057907-Molecular Sequence Data,
pubmed-meshheading:11057907-Peptide Mapping,
pubmed-meshheading:11057907-Polyubiquitin,
pubmed-meshheading:11057907-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11057907-Proteins,
pubmed-meshheading:11057907-Spectrometry, Mass, Matrix-Assisted Laser...,
pubmed-meshheading:11057907-TNF Receptor-Associated Factor 6,
pubmed-meshheading:11057907-Transcription Factors,
pubmed-meshheading:11057907-Ubiquitin-Conjugating Enzymes,
pubmed-meshheading:11057907-Ubiquitin-Protein Ligases,
pubmed-meshheading:11057907-Ubiquitins
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pubmed:year |
2000
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pubmed:articleTitle |
Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain.
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pubmed:affiliation |
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas 75390, 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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