Autoubiquitination of TRIM26 links TBK1 to NEMO in RLR-mediated innate antiviral immune response
Autoubiquitination of TRIM26 links TBK1 to NEMO in RLR-mediated innate antiviral immune response
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TRIM26 的自身泛素化在 RLR 介导的先天抗病毒免疫反应中将 TBK1 与 NEMO 连接起来
DOI：
10.1093/jmcb/mjv068
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发表时间：
2016-02-01
影响因子：
5.5
通讯作者：
Wang, Yan-Yi
中科院分区：
文献类型：
--
作者：
Ran, Yong;Zhang, Jing;Wang, Yan-Yi
转录因子IRF3和NF-kappa B是许多参与抗病毒先天免疫反应的基因的表达所必需的，包括I型干扰素（ifn）和促炎细胞因子。目前已经确定TBK1是参与多种模式识别受体（PRRs）下游介导IRF3磷酸化和激活的重要激酶，但TBK1激活的确切机制尚未完全阐明。在这里，我们发现TRIM26是RNA病毒触发的先天免疫反应的重要调节因子。TRIM26的敲低损害了病毒触发的IRF3、NF-kappa B激活、ifn - β诱导和细胞抗病毒反应。TRIM26与TBK1具有物理相关性，不受病毒感染的影响。TRIM26作为一种E3连接酶，在病毒感染后发生自体泛素化。泛素化的TRIM26随后与NEMO结合，从而桥接TBK1-NEMO相互作用，这对于TBK1招募到VISA信号体和TBK1的激活至关重要。我们的研究结果表明，TRIM26是针对RNA病毒的先天免疫应答的重要调节因子，它通过将TBK1桥接到NEMO并介导TBK1的激活而起作用。
The transcription factors IRF3 and NF-kappa B are required for the expression of many genes involved in antiviral innate immune response, including type I interferons (IFNs) and proinflammatory cytokines. It is well established that TBK1 is an essential kinase engaged downstream of multiple pattern-recognition receptors (PRRs) to mediate IRF3 phosphorylation and activation, whereas the precise mechanisms of TBK1 activation have not been fully elucidated yet. Here, we identified tripartite motif 26 (TRIM26) as an important regulator for RNA virus-triggered innate immune response. Knockdown of TRIM26 impaired virus-triggered IRF3, NF-kappa B activation, IFN-beta induction, and cellular antiviral response. TRIM26 was physically associated with TBK1 independent of viral infection. As an E3 ligase, TRIM26 underwent autoubiquitination upon viral infection. Ubiquitinated TRIM26 subsequently associated with NEMO, thus bridging TBK1-NEMO interaction, which is critical for the recruitment of TBK1 to the VISA signalsome and activation of TBK1. Our findings suggest that TRIM26 is an important regulator of innate immune responses against RNA viruses, which functions by bridging TBK1 to NEMO and mediating the activation of TBK1.