Tumor necrosis factor receptor- associated factor 6 (TRAF6) regulation of development, function, and homeostasis of the immune system.
Tumor necrosis factor receptor- associated factor 6 (TRAF6) regulation of development, function, and homeostasis of the immune system.
复制标题
免疫系统的发育，功能和稳态调节肿瘤坏死因子受体6（TRAF6）。
DOI：
10.1111/imr.12302
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发表时间：
2015-07
影响因子：
8.7
通讯作者：
Choi Y
中科院分区：
文献类型：
--
作者：
Walsh MC;Lee J;Choi Y
肿瘤坏死因子受体相关因子6(TRAF6)是一种接头蛋白，通过其TRAF结构域和具有非常规E3泛素连接酶活性的环指结构域介导广泛的蛋白质-蛋白质相互作用。TRAF6在近20年前首次被发现是IL-1受体(IL-1R)介导的NFκB活化的中介物，后来被确认为具有免疫调节功能的多个受体家族的下游成员，包括TNFR超家族成员、Toll样受体(Toll-like Receptor，TLR)家族成员、肿瘤生长因子-β受体(TGFR-βR)和T细胞受体(TcR)。除核因子κB外，TRAF6还可直接激活丝裂原活化蛋白激酶、磷脂酰肌醇3-激酶和干扰素调节因子途径。在免疫系统中，TRAF6介导的信号已被证明对B细胞、T细胞和髓系细胞(包括巨噬细胞、树突状细胞和破骨细胞)的发育、稳态和/或激活以及胸腺和次级淋巴组织的器官发生至关重要。在多种细胞环境中，TRAF6的功能不仅对于免疫系统的正确激活至关重要，而且对于维持免疫耐受也是必不可少的，最近的工作已经开始识别TRAF6的上下文特异性机制，涉及调控蛋白质相互作用和microRNAs对信使RNA的调控。
Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) is an adaptor protein that mediates a wide array of protein-protein interactions via its TRAF domain and a RING finger domain that possesses non-conventional E3 ubiquitin ligase activity. First identified nearly two decades ago as a mediator of IL-1 receptor (IL-1R)-mediated activation of NFκB, TRAF6 has since been identified as an actor downstream of multiple receptor families with immunoregulatory functions, including members of the TNFR superfamily, the toll-like receptor (TLR) family, tumor growth factor-β receptors (TGFβR), and T cell receptor (TCR). In addition to NFκB, TRAF6 may also direct activation of mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and interferon regulatory factor (IRF) pathways. In the context of the immune system, TRAF6-mediated signals have proven critical for the development, homeostasis, and/or activation of B cells, T cells, and myeloid cells, including macrophages, dendritic cells, and osteoclasts, as well as for organogenesis of thymic and secondary lymphoid tissues. In multiple cellular contexts, TRAF6 function is essential not only for proper activation of the immune system, but also for maintaining immune tolerance, and more recent works have begun to identify mechanisms of contextual specificity for TRAF6, involving both regulatory protein interactions, and messenger RNA regulation by microRNAs.