rdf:type |
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lifeskim:mentions |
umls-concept:C0033684,
umls-concept:C0037083,
umls-concept:C0079904,
umls-concept:C0439855,
umls-concept:C0449432,
umls-concept:C1179435,
umls-concept:C1524073,
umls-concept:C1539081,
umls-concept:C1548799,
umls-concept:C1705248,
umls-concept:C1710082,
umls-concept:C1998811
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pubmed:issue |
6
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pubmed:dateCreated |
2010-7-8
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pubmed:abstractText |
The tumor necrosis factor receptor (TNFR) superfamily mediates signals critical for regulation of the immune system. One family member, CD40, is important for the efficient activation of antibody-producing B cells and other antigen-presenting cells. The molecules and mechanisms that mediate CD40 signaling are only partially characterized. Proteins known to interact with the cytoplasmic domain of CD40 include members of the TNF receptor-associated factor (TRAF) family, which regulate signaling and serve as links to other signaling molecules. To identify additional proteins important for CD40 signaling, we used a combined stimulation/immunoprecipitation procedure to isolate CD40 signaling complexes from B cells and characterized the associated proteins by mass spectrometry. In addition to known CD40-interacting proteins, we detected SMAC/DIABLO, HTRA2/Omi, and HOIP/RNF31/PAUL/ZIBRA. We found that these previously unknown CD40-interacting partners were recruited in a TRAF2-dependent manner. HOIP is a ubiquitin ligase capable of mediating NF-kappaB activation through the ubiquitin-dependent activation of IKKgamma. We found that a mutant HOIP molecule engineered to lack ubiquitin ligase activity inhibited the CD40-mediated activation of NF-kappaB. Together, our results demonstrate a powerful approach for the identification of signaling molecules associated with cell surface receptors and indicate an important role for the ubiquitin ligase activity of HOIP in proximal CD40 signaling.
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pubmed:grant |
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-10748139,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-10880443,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-10929711,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-10929712,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-11038169,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-11606597,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-12413886,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-12569127,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-12571250,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-12958312,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-14632076,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-14981114,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-15093743,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-16897814,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-17006537,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-17633019,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-17633023,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-17878362,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-18499506,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-18635759,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-18997792,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-19136968,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-19237537,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-20005846,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-6605987,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-8757608,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20614026-8779443
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
|
pubmed:status |
MEDLINE
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pubmed:issn |
1932-6203
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pubmed:author |
|
pubmed:issnType |
Electronic
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pubmed:volume |
5
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
e11380
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pubmed:dateRevised |
2011-9-26
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pubmed:meshHeading |
pubmed-meshheading:20614026-Animals,
pubmed-meshheading:20614026-Antigens, CD40,
pubmed-meshheading:20614026-Carrier Proteins,
pubmed-meshheading:20614026-Cell Line,
pubmed-meshheading:20614026-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:20614026-Immunoprecipitation,
pubmed-meshheading:20614026-Mass Spectrometry,
pubmed-meshheading:20614026-Mice,
pubmed-meshheading:20614026-NF-kappa B,
pubmed-meshheading:20614026-Signal Transduction
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pubmed:year |
2010
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pubmed:articleTitle |
HOIL-1L interacting protein (HOIP) as an NF-kappaB regulating component of the CD40 signaling complex.
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pubmed:affiliation |
Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of America. bruce-hostager@uiowa.edu
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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