MAVS-loaded unanchored Lys63-linked polyubiquitin chains activate the RIG-I-MAVS signaling cascade
文献类型：期刊论文
| 作者 | Liu, Feng1,2,3; Zhuang, Wanxin1,2,3; Song, Bin4; Yang, Yuan1,2,3; Liu, Junqi1,2,3; Zheng, Yi1,2,3; Liu, Bingyu1,2,3; Zheng, Jie4; Zhao, Wei1,2,5; Gao, Chengjiang1,2,3 |
| 刊名 | CELLULAR & MOLECULAR IMMUNOLOGY
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| 出版日期 | 2023-08-15 |
| 页码 | 17 |
| ISSN号 | 1672-7681 |
| 关键词 | MAVS Aggregation Unanchored K63-linked polyubiquitin chains RIG-I USP10 |
| DOI | 10.1038/s41423-023-01065-2 |
| 通讯作者 | Gao, Chengjiang(cgao@sdu.edu.cn) |
| 英文摘要 | 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 CARD(RIG-I)-CARD(MAVS) 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. |
| WOS关键词 | NF-KAPPA-B ; STRUCTURAL BASIS ; RNA RECOGNITION ; UBIQUITIN ; PROTEIN ; DEUBIQUITINATION ; COMPLEX ; BINDING ; LIGASE ; USP10 |
| 资助项目 | National Natural Science Foundation of China ; National Key Research and Development Program ; Natural Science Foundation of Shandong Province ; China Postdoctoral Science Foundation ; Postdoctoral Innovation Project of Shandong Province ; [31730026] ; [81930039] ; [32000633] ; [2021YFC2300603] ; [ZR2020QH136] ; [2020M682187] ; [202002012] |
| WOS研究方向 | Immunology |
| 语种 | 英语 |
| 出版者 | CHIN SOCIETY IMMUNOLOGY |
| WOS记录号 | WOS:001048395900003 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306968]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Gao, Chengjiang |
| 作者单位 | 1.Shandong Univ, Key Lab Infect & Immun Shandong Prov, Jinan 250012, Shandong, Peoples R China 2.Shandong Univ, Minist Educ, Key Lab Expt Teratol, Jinan 250012, Shandong, Peoples R China 3.Shandong Univ, Sch Biomed Sci, Dept Immunol, Jinan 250012, Shandong, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 5.Shandong Univ, Sch Biomed Sci, Dept Pathogen Biol, Jinan 250012, Shandong, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Feng,Zhuang, Wanxin,Song, Bin,et al. MAVS-loaded unanchored Lys63-linked polyubiquitin chains activate the RIG-I-MAVS signaling cascade[J]. CELLULAR & MOLECULAR IMMUNOLOGY,2023:17. |
| APA | Liu, Feng.,Zhuang, Wanxin.,Song, Bin.,Yang, Yuan.,Liu, Junqi.,...&Gao, Chengjiang.(2023).MAVS-loaded unanchored Lys63-linked polyubiquitin chains activate the RIG-I-MAVS signaling cascade.CELLULAR & MOLECULAR IMMUNOLOGY,17. |
| MLA | Liu, Feng,et al."MAVS-loaded unanchored Lys63-linked polyubiquitin chains activate the RIG-I-MAVS signaling cascade".CELLULAR & MOLECULAR IMMUNOLOGY (2023):17. |
入库方式： OAI收割
来源：上海药物研究所
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