TRIM41 is required to innate antiviral response by polyubiquitinating BCL10 and recruiting NEMO  

作　　者：Zhou Yu Xuelian Li Mingjin Yang Jiaying Huang Qian Fang Jianjun Jia Zheng Li Yan Gu Taoyong Chen Xuetao Cao 

机构地区：[1]Center for Systems Medicine,Department of Immunology,Institute of Basic Medical Sciences,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100005,China [2]Suzhou Institute of Systems Medicine,Suzhou 215123 Jiangsu,China [3]National Key Laboratory of Medical Immunology&Institute of Immunology,Second Military Medical University,Shanghai 200433,China [4]Institute of Immunology,Zhejiang University School of Medicine,Hangzhou 310058,China [5]College of Life Science,Nankai University,Tianjin 300071,China

出　　处：《Signal Transduction and Targeted Therapy》2021年第3期1057-1068,共12页信号转导与靶向治疗（英文）

基　　金：supported by grants from the National Natural Science Foundation of China(31770937,31970848,82001677,31970892,81788101,31570914,and 81222039);National Key R&D Program of China(2018YFA0507401);the"Shuguang Program"of the Shanghai Education Development Foundation and the Shanghai Municipal Education Commission(15SG32);the Program of Shanghai Subject Chief Scientist(18XD1405200).

摘　　要：Sensing of pathogenic nucleic acids by pattern recognition receptors(PRR)not only initiates anti-microbe defense but causes inflammatory and autoimmune diseases.E3 ubiquitin ligase(s)critical in innate response need to be further identified.Here we report that the tripartite motif-containing E3 ubiquitin ligase TRIM41 is required to innate antiviral response through facilitating pathogenic nucleic acids-triggered signaling pathway.TRIM41 deficiency impairs the production of inflammatory cytokines and type I interferons in macrophages after transfection with nucleic acid-mimics and infection with both DNA and RNA viruses.In vivo,TRIM41 deficiency leads to impaired innate response against viruses.Mechanistically,TRIM41 directly interacts with BCL10(B cell lymphoma 10),a core component of CARD proteins-BCL10—MALT1(CBM)complex,and modifies the Lys63-linked polyubiquitylation of BCL10,which,in turn,hubs NEMO for activation of NF-kB and TANK-binding kinase 1(TBK1)—interferon regulatory factor 3(IRF3)pathways.Our study suggests that TRIM41 is the potential universal E3 ubiquitin ligase responsible for Lys63 linkage of BCL10 during innate antiviral response,adding new insight into the molecular mechanism for the control of innate antiviral response.

关 键 词：BCL10 UBIQUITIN IMPAIRED 

分 类 号：R392[医药卫生—免疫学]