Department of Gastroenterology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China.
Emergency Department, The Aerospace Central Hospital, Beijing, 100049, China.
Mol Immunol. 2022 Mar;143:1-6. doi: 10.1016/j.molimm.2021.12.021. Epub 2022 Jan 3.
TANK-binding kinase 1 (TBK1) plays a pivotal role in antiviral innate immunity. TBK1 mediates the activation of interferon regulatory factor (IRF) 3, leading to the induction of type I IFNs (IFN-α/β) and of NF-κB signal transduction following viral infections. TBK1 must be tightly regulated to effectively control viral infections and maintain immune homeostasis. Here, we found that E3 ubiquitin ligase RNF19a mediated K48-linked ubiquitination and proteasomal degradation of TBK1. Specifically, the silence of RNF19a enhanced the production of type I interferons and suppressed RNA viral replication. Our results uncover that RNF19a acts as a negative mediator in the RIG-I signaling pathway to attenuate antiviral immune responses and suggest RNF19a as a potential therapy target in clinical infectious and inflammatory diseases.
TANK 结合激酶 1（TBK1）在抗病毒先天免疫中发挥关键作用。TBK1 介导干扰素调节因子（IRF）3 的激活，导致在病毒感染后诱导 I 型干扰素（IFN-α/β）和 NF-κB 信号转导。TBK1 必须受到严格的调控，以有效地控制病毒感染并维持免疫稳态。在这里，我们发现 E3 泛素连接酶 RNF19a 介导了 TBK1 的 K48 连接泛素化和蛋白酶体降解。具体而言，沉默 RNF19a 增强了 I 型干扰素的产生并抑制了 RNA 病毒的复制。我们的结果揭示了 RNF19a 作为 RIG-I 信号通路中的负调节剂，可减弱抗病毒免疫反应，并提示 RNF19a 可作为临床感染和炎症性疾病的潜在治疗靶点。
