Papers by Lawrence Pfeffer
Journal of Biological Chemistry, May 1, 2008
Type I interferons (IFNs) play critical roles in the host defense by modulating gene expression t... more Type I interferons (IFNs) play critical roles in the host defense by modulating gene expression through the IFN-dependent activation of STAT and NFB transcription factors. Previous studies established that IFN activates NFB through a classical NFB pathway that results in IB␣ degradation and formation of p50-containing NFB complexes, as well as an alternative pathway that involves NFB-inducing kinase and TRAF2, which results in the formation of p52-containing NFB complexes. In this study, we examined the interaction of TRAF proteins with the type I IFN receptor. We found that TRAF2 was directly coupled to the signal-transducing IFNAR1 subunit of the IFN receptor. By immunoprecipitation, overexpression of epitopetagged IFNAR1 constructs, and glutathione S-transferase pulldown experiments, we demonstrate that TRAF2 rapidly binds to the IFNAR1 subunit of the IFN receptor upon IFN binding. The membrane proximal half of the IFNAR1 subunit was found to directly bind TRAF2. Moreover, analysis of mouse embryo fibroblasts derived from TRAF2 knock-out mice demonstrated that TRAF2 plays a critical role in the activation of the alternative NFB pathway by IFN, but not the classical NFB pathway, as well as in the antiviral action of IFN. Our results place TRAF2 directly in the signaling pathway transduced through the IFNAR1 subunit of the IFN receptor. These findings provide an important insight into the molecular mechanisms by which IFN generates signals to induce its biological effects.
A Novel Role for NF‐kB p50 and p65 Proteins in Interferon Signaling and Antiviral Activity
The FASEB Journal, Mar 1, 2006
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Papers by Lawrence Pfeffer