The function of TRADD in signaling through tumor necrosis factor receptor 1 and TRIF-dependent Toll-like receptors.

TitleThe function of TRADD in signaling through tumor necrosis factor receptor 1 and TRIF-dependent Toll-like receptors.
Publication TypeJournal Article
Year of Publication2008
AuthorsPobezinskaya YL, Kim Y-S, Choksi S, Morgan MJ, Li T, Liu C, Liu Z
JournalNat Immunol
Volume9
Issue9
Pagination1047-54
Date Published2008 Sep
ISSN1529-2916
KeywordsAnimals, Fibroblasts, Macrophages, Mice, Mitogen-Activated Protein Kinases, Signal Transduction, TNF Receptor-Associated Death Domain Protein, TNF Receptor-Associated Factor 1, Toll-Like Receptors, Tumor Necrosis Factor Receptor-Associated Peptides and Proteins, Ubiquitin
Abstract

The physiological function of the adaptor protein TRADD remains unclear because of the unavailability of a TRADD-deficient animal model. By generating TRADD-deficient mice, we found here that TRADD serves an important function in tumor necrosis factor receptor 1 (TNFR1) signaling by orchestrating the formation of TNFR1 signaling complexes. TRADD was essential for TNFR1 signaling in mouse embryonic fibroblasts but was partially dispensable in macrophages; abundant expression of the adaptor RIP in macrophages may have allowed some transmission of TNFR1 signals in the absence of TRADD. Although morphologically normal, TRADD-deficient mice were resistant to toxicity induced by TNF, lipopolysaccharide and polyinosinic-polycytidylic acid. TRADD was also required for TRIF-dependent Toll-like receptor signaling in mouse embryonic fibroblasts but not macrophages. Our findings definitively establish the biological function of TRADD in TNF signaling.

DOI10.1038/ni.1639
Alternate JournalNat. Immunol.
PubMed ID18641653