Targeting signaling factors for degradation, an emerging mechanism for TRAF functions.

Targeting signaling factors for degradation, an emerging mechanism for TRAF functions.
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DOI:
10.1111/imr.12311
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发表时间:
2015-07
影响因子:
8.7
通讯作者:
Sun SC
Sun SC
中科院分区:
医学1区
文献类型:
--
作者:
Yang XD;Sun SC

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肿瘤坏死因子受体(TNFR)相关因子(TRAF)形成了一个蛋白质家族,最为人所知的是TNFR的信号转导衔接子。然而,新出现的证据表明,TRAF蛋白,特别是TRAF 2和TRAF 3,也通过控制细胞内信号传导因子的命运来调节信号转导。TRAF 2和TRAF 3在这方面的公认功能是介导NF-κ B诱导激酶(NIK)的泛素依赖性降解,这是控制NIK调节的非经典NF-κB信号通路所需的作用。TRAF 2和TRAF 3与E3遍在蛋白连接酶cIAP(cIAP 1或cIAP 2)形成复合物,其中TRAF 3作为NIK结合衔接子。最近的证据表明,cIAP-TRAF 2-TRAF 3 E3复合物还靶向泛素依赖性降解的其他信号传导因子,从而调节免疫和炎症反应的重要方面。这篇综述提供了这一泛素化系统的信号功能的历史方面和新的见解。
Tumor necrosis factor receptor (TNFR)-associated factors (TRAFs) form a family of proteins that are best known as signaling adapters of TNFRs. However, emerging evidence suggests that TRAF proteins, particularly TRAF2 and TRAF3, also regulate signal transduction by controlling the fate of intracellular signaling factors. A well-recognized function of TRAF2 and TRAF3 in this aspect is to mediate ubiquitin-dependent degradation of NF-κB-inducing kinase (NIK), an action required for the control of NIK-regulated noncanonical NF-κB signaling pathway. TRAF2 and TRAF3 form a complex with the E3 ubiquitin ligase cIAP (cIAP1 or cIAP2), in which TRAF3 serves as the NIK-binding adapter. Recent evidence suggests that the cIAP-TRAF2-TRAF3 E3 complex also targets additional signaling factors for ubiquitin-dependent degradation, thereby regulating important aspects of immune and inflammatory responses. This review provides both historical aspects and new insights into the signaling functions of this ubiquitination system.
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