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


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.

SUBMITTER: Pobezinskaya YL 

PROVIDER: S-EPMC2577920 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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

Pobezinskaya Yelena L YL   Kim You-Sun YS   Choksi Swati S   Morgan Michael J MJ   Li Tao T   Liu Chengyu C   Liu Zhenggang Z  

Nature immunology 20080720 9


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  ...[more]

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