Journal article
HOIL-1L Interacting Protein (HOIP) as an NF-κB Regulating Component of the CD40 Signaling Complex
PloS one, Vol.5(6), p.e11380
2010
DOI: 10.1371/journal.pone.0011380
PMCID: PMC2894856
PMID: 20614026
Abstract
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-κB activation through the ubiquitin-dependent activation of IKKγ. We found that a mutant HOIP molecule engineered to lack ubiquitin ligase activity inhibited the CD40-mediated activation of NF-κB. 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.
Details
- Title: Subtitle
- HOIL-1L Interacting Protein (HOIP) as an NF-κB Regulating Component of the CD40 Signaling Complex
- Creators
- Bruce S HostagerDaniel K FoxDouglas WhittenCurtis G WilkersonBetty A EipperVictor P FranconePaul B RothmanJohn D Colgan
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.5(6), p.e11380
- DOI
- 10.1371/journal.pone.0011380
- PMID
- 20614026
- PMCID
- PMC2894856
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library of Science; San Francisco, USA
- Alternative title
- HOIP in CD40 Signaling
- Language
- English
- Date published
- 2010
- Academic Unit
- Microbiology and Immunology; Anatomy and Cell Biology; Immunology; Internal Medicine
- Record Identifier
- 9984025567802771
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