The Ubiquitin Ligase TRIM56 Regulates Innate Immune Responses to Intracellular Double-Stranded DNA
The Ubiquitin Ligase TRIM56 Regulates Innate Immune Responses to Intracellular Double-Stranded DNA
复制标题
DOI：
10.1016/j.immuni.2010.10.013
复制
发表时间：
2010-11-24
期刊：
影响因子：
32.4
通讯作者：
Akira, Shizuo
中科院分区：
文献类型：
--
作者：
Tsuchida, Tetsuo;Zou, Jian;Akira, Shizuo
先天免疫系统检测暴露于细胞质中的病原体和宿主来源的双链DNA，并诱导I型干扰素（IFN）和其他细胞因子。在这里，我们发现干扰素诱导的三方基序（TRIM） 56是双链dna介导的I型干扰素诱导的调节因子。TRIM56过表达增强了双链DNA刺激后ifn - β启动子的激活，而TRIM56敲低则消除了它。TRIM56与STING相互作用并靶向其进行赖氨酸63连锁泛素化。这种修饰诱导了STING二聚化，这是抗病毒激酶TBK1募集和随后诱导ifn - β的先决条件。综上所述，这些结果表明TRIM56是一种干扰素诱导的E3泛素连接酶，可调节STING赋予双链dna介导的先天免疫反应。
The innate immune system detects pathogen- and host-derived double-stranded DNA exposed to the cytosol and induces type I interferon (IFN) and other cytokines. Here, we identified interferon-inducible tripartite-motif (TRIM) 56 as a regulator of double-stranded DNA-mediated type I interferon induction. TRIM56 overexpression enhanced IFN-beta promoter activation after double-stranded DNA stimulation whereas TRIM56 knockdown abrogated it. TRIM56 interacted with STING and targeted it for lysine 63-linked ubiquitination. This modification induced STING dimerization, which was a prerequisite for recruitment of the antiviral kinase TBK1 and subsequent induction of IFN-beta. Taken together, these results indicate that TRIM56 is an interferon-inducible E3 ubiquitin ligase that modulates STING to confer double-stranded DNA-mediated innate immune responses.