TRAF molecules in cell signaling and in human diseases.
TRAF molecules in cell signaling and in human diseases.
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DOI：
10.1186/1750-2187-8-7
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发表时间：
2013-06-13
影响因子：
--
通讯作者：
Xie P
中科院分区：
文献类型：
--
作者：
Xie P
肿瘤坏死因子受体（TNF-R）相关因子（TRAF）细胞内蛋白家族最初被确定为直接结合到TNF-R超家族受体的细胞质区域的信号接头。在过去的十年中，发现使用TRAFs进行信号传导的受体家族迅速扩大。这些包括toll样受体（TLRs）、nod样受体（NLRs）、rig - i样受体（rlr）、T细胞受体、IL-1受体家族、IL-17受体、IFN受体和tgf - β受体。除了作为接头蛋白的作用外，大多数TRAFs还作为E3泛素连接酶来激活下游信号事件。traf依赖的信号通路通常会导致核因子-κ b （NF-κ b）、丝裂原活化蛋白激酶（MAPKs）或干扰素调节因子（irf）的激活。从种系和细胞特异性TRAF缺陷小鼠中获得的令人信服的证据表明，每种TRAF都发挥着不可或缺和非冗余的生理作用，调节先天和适应性免疫、胚胎发育、组织稳态、应激反应和骨代谢。值得注意的是，越来越多的证据表明TRAFs与人类疾病（如癌症和自身免疫性疾病）的发病机制有关，这引发了对TRAFs研究的新的认识和兴趣。本文综述了目前对trf的认识，重点介绍了trf分子在信号传导和人类疾病中的最新发现。
The tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) family of intracellular proteins were originally identified as signaling adaptors that bind directly to the cytoplasmic regions of receptors of the TNF-R superfamily. The past decade has witnessed rapid expansion of receptor families identified to employ TRAFs for signaling. These include Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like receptors (RLRs), T cell receptor, IL-1 receptor family, IL-17 receptors, IFN receptors and TGFβ receptors. In addition to their role as adaptor proteins, most TRAFs also act as E3 ubiquitin ligases to activate downstream signaling events. TRAF-dependent signaling pathways typically lead to the activation of nuclear factor-κBs (NF-κBs), mitogen-activated protein kinases (MAPKs), or interferon-regulatory factors (IRFs). Compelling evidence obtained from germ-line and cell-specific TRAF-deficient mice demonstrates that each TRAF plays indispensable and non-redundant physiological roles, regulating innate and adaptive immunity, embryonic development, tissue homeostasis, stress response, and bone metabolism. Notably, mounting evidence implicates TRAFs in the pathogenesis of human diseases such as cancers and autoimmune diseases, which has sparked new appreciation and interest in TRAF research. This review presents an overview of the current knowledge of TRAFs, with an emphasis on recent findings concerning TRAF molecules in signaling and in human diseases.