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

被引：171

作者：

Pobezinskaya, Yelena L. ^{[1
]}

Kim, You-Sun ^{[1
]}

Choksi, Swati ^{[1
]}

Morgan, Michael J. ^{[1
]}

Li, Tao ^{[1
]}

Liu, Chengyu ^{[2
]}

Liu, Zhenggang ^{[1
]}

机构：

[1] NCI, Cell & Canc Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA

[2] NHLBI, Transgen Core Facil, Natl Inst Hlth, Bethesda, MD 20892 USA

来源：

NATURE IMMUNOLOGY | 2008年 / 9卷 / 09期

关键词：

D O I：

10.1038/ni.1639

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：1047 / 1054

页数：8

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