仙台病毒
脱氮酶
先天免疫系统
细胞生物学
基因敲除
生物
磷酸化
干扰素
免疫系统
泛素
信号转导
免疫沉淀
调节器
转录因子
病毒
免疫学
抗体
生物化学
基因
作者
Liqun Chen,Rong-Chun Tang,Jiawei Liang,Wei Zhao,Shuang-Shuang Yu,Ran-Ran Yao,Rui Xu,Ao Zhang,Shijin Geng,Xiuyuan Sun,Qi Ge,Jun Zhang
标识
DOI:10.1016/j.intimp.2023.110040
摘要
The innate immune responses are tightly regulated to ensure effective clearance of invading pathogens and avoid excessive inflammation. Ubiquitination and deubiquitination are important post-translational modifications in antiviral immune responses. Here, we discovered deubiquitinase USP47 as a novel negative immune system regulator. Overexpression of USP47 repressed Sendai virus, poly(I:C) and poly(dA:dT)-induced ISRE and IFN-β activation, along with reduced IFNB1 transcription and enhanced viral replication. Knockdown of USP47 expression had the opposite effects. Dual-luciferase and phosphorylation assays showed that USP47 targeted downstream of MAVS and upstream of TBK1. Additional co-immunoprecipitation assays suggested that USP47 interacted with TRAF3 and TRAF6. Importantly, USP47 removed K63-linked polyubiquitin chains from TRAF3 and TRAF6. Hence, we describe a novel modulator of the antiviral innate immune response, USP47, which removes K63-linked polyubiquitins from TRAF3 and TRAF6, leading to reduced type I IFN signaling.
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