E3 ubiquitin ligase RNF128 promotes innate antiviral immunity through K63-linked ubiquitination of TBK1
E3 ubiquitin ligase RNF128 promotes innate antiviral immunity through K63-linked ubiquitination of TBK1
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E3 泛素连接酶 RNF128 通过 K63 连接的 TBK1 泛素化促进先天抗病毒免疫
DOI：
10.1038/ni.3588
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发表时间：
2016-12-01
影响因子：
30.5
通讯作者：
Gao, Chengjiang
中科院分区：
文献类型：
--
作者：
Song, Guanhua;Liu, Bingyu;Gao, Chengjiang
TBK 1对于干扰素-β（IFN-β）的产生和先天性抗病毒免疫至关重要。在这里，我们确定了T细胞无能相关的E3泛素连接酶RNF 128作为TBK 1激活的正调节因子。RNF 128通过其蛋白酶相关（PA）结构域与TBK 1直接相互作用，并催化TBK 1的K63连接的多泛素化，这导致TBK 1活化、IRF 3活化和IFN-β产生。在体外和体内，RNF 128表达的缺陷减弱了IRF 3活化、IFN-β产生和对RNA和DNA病毒的先天性抗病毒免疫应答。我们的研究将RNF 128鉴定为K63连接的泛素化和TBK 1活化的E3连接酶，并描绘了RNF 128以前未被识别的功能。
TBK1 is essential for interferon-beta (IFN-beta) production and innate antiviral immunity. Here we identified the T cell anergy-related E3 ubiquitin ligase RNF128 as a positive regulator of TBK1 activation. RNF128 directly interacted with TBK1 through its protease-associated (PA) domain and catalyzed the K63-linked polyubiquitination of TBK1, which led to TBK1 activation, IRF3 activation and IFN-beta production. Deficiency of RNF128 expression attenuated IRF3 activation, IFN-beta production and innate antiviral immune responses to RNA and DNA viruses, in vitro and in vivo. Our study identified RNF128 as an E3 ligase for K63-linked ubiquitination and activation of TBK1 and delineated a previously unrecognized function for RNF128.