TRAF-interacting protein (TRIP) negatively regulates IFN-β production and antiviral response by promoting proteasomal degradation of TANK-binding kinase 1.
TRAF-interacting protein (TRIP) negatively regulates IFN-β production and antiviral response by promoting proteasomal degradation of TANK-binding kinase 1.
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DOI：
10.1084/jem.20120024
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发表时间：
2012-09-24
期刊：
影响因子：
--
通讯作者：
Gao C
中科院分区：
文献类型：
--
作者：
Zhang M;Wang L;Zhao X;Zhao K;Meng H;Zhao W;Gao C
TRAF相互作用蛋白(TRIP)通过促进K48连接的泛素化和蛋白酶体的降解，负性调节TLR3/4和RIG-I诱导的干扰素-β信号转导。TABK1在Toll样受体和维甲酸诱导基因I(RIG-I)介导的I型干扰素(干扰素；干扰素-α/β)诱导和宿主抗病毒反应中起重要作用。TBK1活性如何受到负面调控仍在很大程度上尚不清楚。我们报道了肿瘤坏死因子受体相关因子相互作用蛋白(TRIP)促进Tbk1蛋白酶体降解，并抑制TLR3/4和RIG-I诱导的干扰素-β信号转导。TRIP基因敲除导致TLR3/4和Rig-I激活的原代巨噬细胞中干扰素调节因子3(IRF3)的激活和干扰素-β的表达增强，而TRIP过表达则相反。TRIP持续抑制仙台病毒感染诱导IRF3激活和干扰素-β的产生，并促进水疱性口炎病毒的复制。作为一种E3泛素连接酶，TRIP通过直接结合并促进Tbk1的K48连接的多泛素化，负向调节细胞内的Tbk1的水平。因此，我们确定TRIP是TLR3/4和RIG-I触发的抗病毒反应的负调控因子，并建议TRIP作为干预干扰素-β产生不受控制的疾病的潜在靶点。
TRAF-interacting protein (TRIP) negatively regulates TLR3/4- and RIG-I–induced IFN-β signaling by promoting K48-linked ubiquitination and proteasomal degradation of TBK1. TANK-binding kinase 1 (TBK1) plays an essential role in Toll-like receptor (TLR)– and retinoic acid–inducible gene I (RIG-I)–mediated induction of type I interferon (IFN; IFN-α/β) and host antiviral responses. How TBK1 activity is negatively regulated remains largely unknown. We report that TNF receptor-associated factor (TRAF)–interacting protein (TRIP) promotes proteasomal degradation of TBK1 and inhibits TLR3/4- and RIG-I–induced IFN-β signaling. TRIP knockdown resulted in augmented activation of IFN regulatory factor 3 (IRF3) and enhanced expression of IFN-β in TLR3/4- and RIG-I–activated primary peritoneal macrophages, whereas overexpression of TRIP had opposite effects. Consistently, TRIP impaired Sendai virus (SeV) infection–induced IRF3 activation and IFN-β production and promoted vesicular stomatitis virus (VSV) replication. As an E3 ubiquitin ligase, TRIP negatively regulated the cellular levels of TBK1 by directly binding to and promoting K48-linked polyubiquitination of TBK1. Therefore, we identified TRIP as a negative regulator in TLR3/4- and RIG-I–triggered antiviral responses and suggested TRIP as a potential target for the intervention of diseases with uncontrolled IFN-β production.
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DOI：
10.1084/jem.20031187
发表时间：
2003-12-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Regamey A;Hohl D;Liu JW;Roger T;Kogerman P;Toftgard R;Huber M
通讯作者：
Huber M
影响因子：
32.4
作者：
Lei, Cao-Qi;Zhong, Bo;Shu, Hong-Bing
通讯作者：
Shu, Hong-Bing
NLRP4 通过泛素连接酶 DTX4 靶向激酶 TBK1 进行降解，从而负调节 I 型干扰素信号传导
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
32.4
作者：
Doyle, SE;Vaidya, SA;Cheng, G
通讯作者：
Cheng, G
影响因子：
30.5
作者：
Wang, Chen;Chen, Taoyong;Cao, Xuetao
通讯作者：
Cao, Xuetao