E3 泛素连接酶 RNF128 通过 TBK1 的 K63 链接泛素化促进先天抗病毒免疫。
E3 ubiquitin ligase RNF128 promotes innate antiviral immunity through K63-linked ubiquitination of TBK1.
机构信息
Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University the School of Medicine, Jinan, China.
Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, China.
出版信息
Nat Immunol. 2016 Dec;17(12):1342-1351. doi: 10.1038/ni.3588. Epub 2016 Oct 24.
TBK1 is essential for interferon-β (IFN-β) 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-β production. Deficiency of RNF128 expression attenuated IRF3 activation, IFN-β 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.
TBK1 对于干扰素-β（IFN-β）的产生和先天抗病毒免疫至关重要。在这里，我们鉴定了与 T 细胞无能相关的 E3 泛素连接酶 RNF128 是 TBK1 激活的正调节剂。RNF128 通过其蛋白酶相关（PA）结构域与 TBK1 直接相互作用，并催化 TBK1 的 K63 连接多泛素化，导致 TBK1 激活、IRF3 激活和 IFN-β 的产生。RNF128 表达的缺失减弱了 IRF3 的激活、IFN-β 的产生和对 RNA 和 DNA 病毒的先天抗病毒免疫反应，无论是在体外还是体内。我们的研究鉴定了 RNF128 作为 TBK1 的 K63 连接泛素化和激活的 E3 连接酶，并描绘了 RNF128 的一个以前未被认识的功能。
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