The Adaptor Protein MITA Links Virus-Sensing Receptors to IRF3 Transcription Factor Activation
The Adaptor Protein MITA Links Virus-Sensing Receptors to IRF3 Transcription Factor Activation
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接头蛋白 MITA 将病毒感应受体与 IRF3 转录因子激活连接起来
DOI：
10.1016/j.immuni.2008.09.003
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发表时间：
2008-10-17
期刊：
影响因子：
32.4
通讯作者：
Shu, Hong-Bing
中科院分区：
文献类型：
--
作者：
Zhong, Bo;Yang, Yan;Shu, Hong-Bing
病毒感染会触发 NF-kappa B 和 IRF3 等转录因子的激活，这些转录因子协同诱导 I 型干扰素 (IFN) 并引发先天抗病毒反应。在这里，我们通过表达克隆确定 MITA 是病毒触发的 I 型 IFN 信号转导的关键介质。 MITA 的过表达会激活 IRF3，而 MITA 的敲低会抑制病毒触发的 IRF3 激活、I 型 IFN 的表达和细胞抗病毒反应。 MITA 被发现定位于线粒体外膜，并与 VISA 相关，VISA 是一种线粒体蛋白，在病毒触发的信号传导中充当适配器。 MITA 还与 IRF3 相互作用，并将激酶 TBK1 招募到 VISA 相关复合物中。 MITA 被 TBK1 磷酸化，这是 MITA 介导的 IRF3 激活所必需的。我们的结果表明 MITA 是病毒触发的 IRF3 激活和 IFN 表达的关键介质，并进一步证明了某些线粒体蛋白在先天抗病毒免疫中的重要性。
Viral infection triggers activation of transcription factors such as NF-kappa B and IRF3, which collaborate to induce type I interferons (IFNs) and elicit innate antiviral response. Here, we identified MITA as a critical mediator of virus-triggered type I IFN signaling by expression cloning. Overexpression of MITA activated IRF3, whereas knockdown of MITA inhibited virus-triggered activation of IRF3, expression of type I IFNs, and cellular antiviral response. MITA was found to localize to the outer membrane of mitochondria and to be associated with VISA, a mitochondrial protein that acts as an adaptor in virus-triggered signaling. MITA also interacted with IRF3 and recruited the kinase TBK1 to the VISA-associated complex. MITA was phosphorylated by TBK1, which is required for MITA-mediated activation of IRF3. Our results suggest that MITA is a critical mediator of virus-triggered IRF3 activation and IFN expression and further demonstrate the importance of certain mitochondrial proteins in innate antiviral immunity.