Wajant H, Scheurich P
Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, Stuttgart 70569, Germany.
Int J Biochem Cell Biol. 2001 Jan;33(1):19-32. doi: 10.1016/s1357-2725(00)00064-9.
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-kappaB 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-kappaB 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-kappaB-mediated surviving signals.
肿瘤坏死因子（TNF）是TNF配体家族的原型成员，在炎症过程的调节中起关键作用。TNF通过与含死亡结构域的TNF受体1（TNF-R1）和不含死亡结构域的TNF受体2（TNF-R2）相互作用发挥其功能，这两种受体都是与TNF配体家族互补的受体家族成员。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得到广泛研究。近年来，已鉴定出几种直接或间接与TNF-R1和TNF-R2细胞质结构域相互作用的蛋白质，这为了解这些受体如何与凋亡途径以及导致NF-κB和JNK激活的信号级联反应相联系提供了思路。特别值得关注的是TNF受体相关因子（TRAF）1和2，它们定义了一组新的衔接蛋白，参与TNF受体家族的大多数成员、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是目前特征最明确的TRAF家族成员，在介导TNF-R1诱导的NF-κB和JNK激活中起关键作用。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。本综述重点关注TNF-R1和TNF-R2信号起始的分子机制，特别考虑TRAF 2的作用，并强调该分子对于整合诸如死亡诱导和NF-κB介导存活信号等拮抗途径的重要性。
