Beyond tumor necrosis factor receptor:: TRADD signaling in toll-like receptors
Beyond tumor necrosis factor receptor:: TRADD signaling in toll-like receptors
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DOI：
10.1073/pnas.0806585105
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发表时间：
2008-08-26
影响因子：
11.1
通讯作者：
Mak, Tak W.
中科院分区：
文献类型：
--
作者：
Chen, Nien-Jung;Chio, Iok In Christine;Mak, Tak W.
肿瘤坏死因子受体1相关死亡结构域蛋白（TRADD）是TNF α刺激后招募至TNF受体1（TNFR 1）的核心衔接子。在TRADD缺陷小鼠的细胞中，TNF α介导的细胞凋亡和TNF α刺激的NF-κ B、JNK和ERK活化是缺陷的。TRADD对生发中心形成、DR 3介导的T细胞共刺激和TNF α介导的体内炎症反应也很重要。TRADD缺陷不增强IFN γ-included信号传导。重要的是，TRADD在TLR 3和TLR 4信号传导中具有新的作用。TRADD参与LPS刺激后形成的TLR 4复合物，并且TRADD缺陷型巨噬细胞在体外响应TLR配体显示出受损的细胞因子产生。因此，TRADD是一种多功能蛋白质，对于TNFR 1信号传导和与免疫应答相关的其他信号传导途径都至关重要。
Tumor necrosis factor receptor 1-associated death domain protein (TRADD) is the core adaptor recruited to TNF receptor 1 (TNFR1) upon TNF alpha stimulation. In cells from TRADD-deficient mice, TNF alpha-mediated apoptosis and TNF alpha-stimulated NF-kappa B, JNK, and ERK activation are defective. TRADD is also important for germinal center formation, DR3-mediated costimulation of T cells, and TNF alpha-mediated inflammatory responses in vivo. TRADD deficiency does not enhance IFN gamma-incluced signaling. Importantly, TRADD has a novel role in TLR3 and TLR4 signaling. TRADD participates in the TLR4 complex formed upon LPS stimulation, and TRADD-deficient macrophages show impaired cytokine production in response to TLR ligands in vitro. Thus, TRADD is a multifunctional protein crucial both for TNFR1 signaling and other signaling pathways relevant to immune responses.