HOIL-1L interacting protein (HOIP) as an NF-kappaB regulating component of the CD40 signaling complex
| Autor: | Paul B. Rothman, John D. Colgan, Daniel K. Fox, Victor P. Francone, Betty A. Eipper, Bruce S. Hostager, Douglas Whitten, Curtis G. Wilkerson |
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| Rok vydání: | 2010 |
| Předmět: |
Cell signaling
Immunoprecipitation Immunology lcsh:Medicine Mass Spectrometry Cell Biology/Cell Signaling Cell Line 03 medical and health sciences chemistry.chemical_compound Mice Immunology/Leukocyte Signaling and Gene Expression 0302 clinical medicine Cell surface receptor Biochemistry/Cell Signaling and Trafficking Structures Animals Cell Biology/Leukocyte Signaling and Gene Expression CD40 Antigens lcsh:Science Transcription factor 030304 developmental biology 0303 health sciences Multidisciplinary biology lcsh:R NF-kappa B NF-κB Ubiquitin ligase Cell biology Membrane protein chemistry 030220 oncology & carcinogenesis Immunology/Leukocyte Activation biology.protein lcsh:Q Electrophoresis Polyacrylamide Gel Signal transduction Carrier Proteins Signal Transduction Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 5, Iss 6, p e11380 (2010) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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