HOIL-1L interacting protein (HOIP) as an Nf-κB regulating component of the CD40 signaling complex

Bruce S. Hostager, Daniel K. Fox, Douglas Whitten, Curtis G. Wilkerson, Betty A. Eipper, Victor P. Francone, Paul B Rothman, John D. Colgan

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere11380
JournalPLoS One
Volume5
Issue number6
DOIs
StatePublished - 2010
Externally publishedYes

Fingerprint

ubiquitin
Ubiquitin
Proteins
Ligases
proteins
Chemical activation
ligases
Molecules
receptors
B-lymphocytes
B-Lymphocytes
TNF Receptor-Associated Factor 2
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Cells
Antibody-Producing Cells
antigen-presenting cells
tumor necrosis factors
Tumor Necrosis Factor Receptors
Immune system
Cell Surface Receptors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Hostager, B. S., Fox, D. K., Whitten, D., Wilkerson, C. G., Eipper, B. A., Francone, V. P., ... Colgan, J. D. (2010). HOIL-1L interacting protein (HOIP) as an Nf-κB regulating component of the CD40 signaling complex. PLoS One, 5(6), [e11380]. https://doi.org/10.1371/journal.pone.0011380

HOIL-1L interacting protein (HOIP) as an Nf-κB regulating component of the CD40 signaling complex. / Hostager, Bruce S.; Fox, Daniel K.; Whitten, Douglas; Wilkerson, Curtis G.; Eipper, Betty A.; Francone, Victor P.; Rothman, Paul B; Colgan, John D.

In: PLoS One, Vol. 5, No. 6, e11380, 2010.

Research output: Contribution to journalArticle

Hostager, BS, Fox, DK, Whitten, D, Wilkerson, CG, Eipper, BA, Francone, VP, Rothman, PB & Colgan, JD 2010, 'HOIL-1L interacting protein (HOIP) as an Nf-κB regulating component of the CD40 signaling complex', PLoS One, vol. 5, no. 6, e11380. https://doi.org/10.1371/journal.pone.0011380
Hostager, Bruce S. ; Fox, Daniel K. ; Whitten, Douglas ; Wilkerson, Curtis G. ; Eipper, Betty A. ; Francone, Victor P. ; Rothman, Paul B ; Colgan, John D. / HOIL-1L interacting protein (HOIP) as an Nf-κB regulating component of the CD40 signaling complex. In: PLoS One. 2010 ; Vol. 5, No. 6.
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