Tumor necrosis factor receptor-associated factor (TRAF) 2 and its role in TNF signaling.
Tumor necrosis factor receptor-associated factor (TRAF) 2 and its role in TNF signaling.
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DOI：
10.1016/s1357-2725(00)00064-9
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Harald Wajant;P. Scheurich
中科院分区：
文献类型：
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作者：
Harald Wajant;P. Scheurich
肿瘤坏死因子（TNF）是TNF配体家族的原型成员，并且在炎症过程的调节中具有关键作用。TNF通过与含有死亡结构域的TNF-受体1（TNF-R1）和含有非死亡结构域的TNF-受体2（TNF-R2）相互作用来发挥其功能，这两种受体家族的成员都与TNF配体家族互补。由于TNF受体的原型特征及其对炎症调节的重要性，这些受体所利用的信号转导机制已被广泛研究。近年来，已经鉴定了几种与TNF-R1和TNF-R2的胞质结构域直接或间接相互作用的蛋白质，从而提出了这些受体如何与凋亡途径和导致NF-κB和JNK活化的信号级联连接的想法。特别感兴趣的是TNF受体相关因子（TRAF）1和2，其定义了一组新的衔接蛋白，其参与TNF受体家族、IL-1受体和IL-17受体以及TOLL样受体家族的一些成员的信号转导。TRAF 2是目前最具特征的TRAF家族成员，在介导TNF-R1诱导的NF-κB和JNK活化中具有关键作用。此外，最近的研究表明TRAF 2代表了促凋亡和抗凋亡信号的整合点。本文综述了TNF-R1和TNF-R2抑制信号启动的分子机制，特别是TRAF 2的作用，并强调了该分子在整合死亡诱导和NF-κ B介导的存活信号等拮抗途径中的重要性。
Tumor necrosis factor (TNF) is the prototypic member of the TNF ligand family and has a key role in the regulation of inflammatory processes. TNF exerts its functions by interaction with the death domain-containing TNF-receptor 1 (TNF-R1) and the non-death domain-containing TNF-receptor 2 (TNF-R2), both members of a receptor family complementary to the TNF ligand family. Due to the prototypic features of the TNF receptors and their importance for the regulation of inflammation, the signal transduction mechanisms utilized by these receptors have been extensively studied. Several proteins that interact directly or indirectly with the cytoplasmic domains of TNF-R1 and TNF-R2 have been identified in the recent years giving ideas how these receptors are connected to the apoptotic pathway and the signaling cascades leading to activation of NF-κB and JNK. Of special interest are TNF receptor-associated factor (TRAF) 1 and 2, which defines a novel group of adaptor proteins involved in signal transduction by most members of the TNF receptor family, of IL-1 receptor and IL-17 receptor as well as some members of the TOLL-like receptor family. TRAF 2 is currently the best-characterized TRAF family member, having a key role in mediating TNF-R1-induced activation of NF-κB and JNK. Moreover, recent studies suggest that TRAF 2 represents an integration point for pro- and antiapoptotic signals. This review focuses on the molecular mechanisms that underlay signal initiation by TNF-R1 and TNF-R2, with particular consideration of the role of TRAF 2, and highlights the importance of this molecule for the integration of such antagonizing pathways as death induction and NF-κB-mediated surviving signals.