STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling.
STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling.
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DOI：
10.1038/nature07317
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发表时间：
2008-10-02
期刊：
影响因子：
64.8
通讯作者：
Barber, Glen N.
中科院分区：
文献类型：
--
作者：
Ishikawa, Hiroki;Barber, Glen N.
我们在此报告了在表达克隆后对调节先天免疫信号传导过程的分子 STING（干扰素基因的 STimulator）的鉴定。 STING 包含 5 个假定的跨膜 (TM) 区域，主要驻留在内质网 (ER) 中，能够激活 NF-κB 和 IRF3 转录途径，诱导 I 型 IFN 并在表达后发挥有效的抗病毒状态。相反，STING 的缺失使得小鼠胚胎成纤维细胞 (STING −/−MEF) 极易受到负链病毒感染，包括水泡性口炎病毒 (VSV)。此外，STING 消融消除了细胞内 B 型 DNA 以及疱疹病毒家族成员诱导 IFNβ 的能力，但没有显着影响 Toll 样受体（TLR 途径）。酵母-两种杂交和共免疫沉淀研究表明，STING 与 RIG-I 和 Ssr2/TRAPβ 相互作用，Ssr2/TRAPβ 是易位子相关蛋白 (TRAP) 复合物的成员，是翻译后蛋白质跨内质网易位所必需的。随后发现 TRAPβ 和易位子接头 Sec61β 的 RNAi 消除可抑制 STING 刺激 IFNβ 的能力。因此，除了鉴定出一种新的先天免疫信号调节剂之外，该数据还首次表明易位子在由选定病毒和细胞内DNA激活的先天信号传导途径中的潜在作用。
We report here the identification, following expression cloning, of a molecule, STING (STimulator of INterferon Genes) that regulates innate immune signaling processes. STING, comprising 5 putative transmembrane (TM) regions, predominantly resides in the endoplasmic reticulum (ER) and is able to activate both NF-κB and IRF3 transcription pathways to induce type I IFN and exert a potent anti-viral state following expression. In contrast, loss of STING rendered murine embryonic fibroblasts (STING −/−MEFs) extremely susceptible to negative-stranded virus infection, including vesicular stomatitis virus, VSV. Further, STING ablation abrogated the ability of intracellular B-form DNA, as well as members of the herpes virus family, to induce IFNβ, but did not significantly affect the Toll-like receptor (TLR pathway). Yeast-two hybrid and co-immunprecipitation studies indicated that STING interacts with RIG-I and with Ssr2/TRAPβ, a member of the translocon-associated protein (TRAP) complex required for protein translocation across the ER membrane following translation. RNAi ablation of TRAPβ and translocon adaptor Sec61β was subsequently found to inhibit STING’s ability to stimulate IFNβ. Thus, aside from identifying a novel regulator of innate immune signaling, this data implicates for the first time a potential role for the translocon in innate signaling pathways activated by select viruses as well as intracellular DNA.
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