MAVS-loaded unanchored Lys63-linked polyubiquitin chains activate the RIG-I-MAVS signaling cascade

作     者：Feng Liu Wanxin Zhuang Bin Song Yuan Yang Junqi Liu Yi Zheng Bingyu Liu Jie Zheng Wei Zhao Chengjiang Gao 

作者机构：Key Laboratory of Infection and Immunity of Shandong Province&Key Laboratory for Experimental Teratology of Ministry of EducationShandong UniversityJinan250012ShandongP.R.China Department of ImmunologySchool of Biomedical SciencesShandong UniversityJinan250012ShandongP.R.China Shanghai Institute of Materia MedicaChinese Academy of Sciences201203ShanghaiP.R.China Department of Pathogenic BiologySchool of Biomedical SciencesShandong UniversityJinan250012ShandongP.R.China 

出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)

年 卷 期：2023年第20卷第10期

页      面：1186-1202页

核心收录：

学科分类：1001[医学-基础医学(可授医学、理学学位)] 100102[医学-免疫学] 10[医学] 

基　　金：supported by grants from the National Natural Science Foundation of China(31730026,81930039,32000633) National Key Research and Development Program(2021YFC2300603),Natural Science Foundation of Shandong Province(ZR2020QH136) China Postdoctoral Science Foundation(2020M682187),and Postdoctoral Innovation Project of Shandong Province(202002012) 

主　　题：MAVS Aggregation Unanchored K63-linked polyubiquitin chains RIG-l USP10 

摘      要：The adaptor molecule MAVS forms prion-like aggregates to govern the RIG-I-like receptor(RLR)signaling ***63(K63)-linked polyubiquitination is critical for MAVS aggregation,yet the underlying mechanism and the corresponding E3 ligases and deubiquitinating enzymes(DUBs)remain ***,we found that the K63-linked polyubiquitin chains loaded on MAVS can be directly recognized by RIG-I to initiate RIG-I-mediated MAVS aggregation with the prerequisite of the CARDRIG-I-CARDMAVS ***,many K63-linked polyubiquitin chains attach to MAVS via an unanchored *** identified Ube2N as a major ubiquitin-conjugating enzyme for MAVS and revealed that Ube2N cooperates with the E3 ligase Riplet and TRIM31 to promote the unanchored K63-linked polyubiquitination of *** addition,we identified USP10 as a direct DUB that removes unanchored K63-linked polyubiquitin chains from ***,USP10 attenuates RIG-I-mediated MAVS aggregation and the production of type I *** with a deficiency in USP10 show more potent resistance to RNA virus *** work proposes a previously unknown mechanism for the activation of the RLR signaling cascade triggered by MAVS-attached unanchored K63-linked polyubiquitin chains and establishes the DUB USP10 and the E2:E3 pair Ube2N-Riplet/TRIM31 as a specific regulatory system for the unanchored K63-linked ubiquitination and aggregation of MAVS upon viral infection.