首页|MAVS-loaded unanchored Lys63-linked polyubiquitin chains activate the RIG-I-MAVS signaling cascade
MAVS-loaded unanchored Lys63-linked polyubiquitin chains activate the RIG-I-MAVS signaling cascade
扫码查看
点击上方二维码区域，可以放大扫码查看
原文链接
万方数据
The adaptor molecule MAVS forms prion-like aggregates to govern the RIG-I-like receptor(RLR)signaling cascade.Lys63(K63)-linked polyubiquitination is critical for MAVS aggregation,yet the underlying mechanism and the corresponding E3 ligases and deubiquitinating enzymes(DUBs)remain elusive.Here,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 interaction.Interestingly,many K63-linked polyubiquitin chains attach to MAVS via an unanchored linkage.We 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 MAVS.In addition,we identified USP10 as a direct DUB that removes unanchored K63-linked polyubiquitin chains from MAVS.Consistently,USP10 attenuates RIG-I-mediated MAVS aggregation and the production of type I interferon.Mice with a deficiency in USP10 show more potent resistance to RNA virus infection.Our 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.
Key Laboratory of Infection and Immunity of Shandong Province & Key Laboratory for Experimental Teratology of Ministry of Education,Shandong University,Jinan 250012 Shandong,P.R.China
Department of Immunology,School of Biomedical Sciences,Shandong University,Jinan 250012 Shandong,P.R.China
Shanghai Institute of Materia Medica,Chinese Academy of Sciences,201203 Shanghai,P.R.China
Department of Pathogenic Biology,School of Biomedical Sciences,Shandong University,Jinan 250012 Shandong,P.R.China
展开 >
Shanghai Institute of Biochemistry and Cell Biology,Chinese Academy of SciencesNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Key Research and Development ProgramNatural Science Foundation of Shandong ProvinceChina Postdoctoral Science FoundationPostdoctoral Innovation Project of Shandong Province
万方数据
