| FTRCA1, a Species-Specific Member of finTRIM Family, Negatively Regulates Fish IFN Response through Autophage-Lysosomal Degradation of TBK1 | |
| Wu, Min1,2; Zhao, Xiang1,2; Gong, Xiu-Ying1,2; Wang, Yang1,2; Gui, Jian-Fang1,2,3; Zhang, Yi-Bing1,2,3,4 | |
| Corresponding Author | Zhang, Yi-Bing(ybzhang@ihb.ac.cn) |
| 2019-04-15 | |
| Source Publication | JOURNAL OF IMMUNOLOGY
 |
| ISSN | 0022-1767 |
| Volume | 202Issue:8Pages:2407-2420 |
| Abstract | In mammals, tripartite motif (TRIM) proteins have emerged as pivotal players endowed with, directly, antiviral effects and, indirectly, modulatory capacity of the innate immune response. An unprecedented expansion of TRIM family has occurred in fish; however, the functional role of fish TRIM family members remains largely unknown. In this study, we identify a species-specific TRIM gene from crucian carp Carassius auratus, named FTRCA1, phylogenetically similar to the members of finTRIM, a subfamily of TRIM exclusively in teleost fish. FTRCA1 is induced by IFN and IFN stimuli as a typical IFN-stimulated gene. Overexpression of FTRCA1 negatively regulates IFN antiviral response by inhibition of IRF3 phosphorylation; consistently, knockdown of FTRCA1 results in enhanced levels of IRF3 phosphorylation and also IFN expression following poly(I:C) transfection. Whereas FTRCA1 is associated with several pivotal signaling molecules of RIG-I-like receptor pathway, its association with TBK1 results in autophage-lysosomal degradation of TBK1, thus abrogating the downstream IFN induction. Interestingly, FTRCA1 is phosphorylated by TBK1, but this phosphorylation is not required for downregulation of TBK1 protein. Transfection assays indicate that FTRCA1 is likely an E3 ligase with the requirement of RING finger domain, and deletion of N-terminal RING domain or mutation of seven conservative sites abolishes the negative regulatory function of FTRCA1. Collectively, these results illuminate a novel finTRIM-mediated innate immune modulatory pathway, thus providing insights into species-specific regulation of fish IFN response. |
| DOI | 10.4049/jimmunol.1801645 |
| Funding Organization | National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation ; National Natural Science Foundation ; National Natural Science Foundation ; National Natural Science Foundation ; Freshwater Ecology and Biotechnology Laboratory ; Freshwater Ecology and Biotechnology Laboratory ; Freshwater Ecology and Biotechnology Laboratory ; Freshwater Ecology and Biotechnology Laboratory ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation ; National Natural Science Foundation ; National Natural Science Foundation ; National Natural Science Foundation ; Freshwater Ecology and Biotechnology Laboratory ; Freshwater Ecology and Biotechnology Laboratory ; Freshwater Ecology and Biotechnology Laboratory ; Freshwater Ecology and Biotechnology Laboratory ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation ; National Natural Science Foundation ; National Natural Science Foundation ; National Natural Science Foundation ; Freshwater Ecology and Biotechnology Laboratory ; Freshwater Ecology and Biotechnology Laboratory ; Freshwater Ecology and Biotechnology Laboratory ; Freshwater Ecology and Biotechnology Laboratory ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation ; National Natural Science Foundation ; National Natural Science Foundation ; National Natural Science Foundation ; Freshwater Ecology and Biotechnology Laboratory ; Freshwater Ecology and Biotechnology Laboratory ; Freshwater Ecology and Biotechnology Laboratory ; Freshwater Ecology and Biotechnology Laboratory |
| Indexed By | SCI ; SCI |
| Language | 英语 |
| Funding Project | National Key R&D Program of China[2018YFD0900302] ; National Natural Science Foundation[31572646] ; National Natural Science Foundation[31772875] ; Freshwater Ecology and Biotechnology Laboratory[2016FBZ01] |
| WOS Research Area | Immunology |
| WOS Subject | Immunology |
| WOS ID | WOS:000463861100021 |
| WOS Keyword | ANTIVIRAL IMMUNE-RESPONSE ; INNATE IMMUNE ; ZEBRAFISH IRF1 ; TRIM FAMILY ; INTERFERON ; EXERTS ; ACTIVATION ; ROLES ; MOTIF ; PROTEINS |
| Publisher | AMER ASSOC IMMUNOLOGISTS |
| Funding Organization | National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation ; National Natural Science Foundation ; National Natural Science Foundation ; National Natural Science Foundation ; Freshwater Ecology and Biotechnology Laboratory ; Freshwater Ecology and Biotechnology Laboratory ; Freshwater Ecology and Biotechnology Laboratory ; Freshwater Ecology and Biotechnology Laboratory ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation ; National Natural Science Foundation ; National Natural Science Foundation ; National Natural Science Foundation ; Freshwater Ecology and Biotechnology Laboratory ; Freshwater Ecology and Biotechnology Laboratory ; Freshwater Ecology and Biotechnology Laboratory ; Freshwater Ecology and Biotechnology Laboratory ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation ; National Natural Science Foundation ; National Natural Science Foundation ; National Natural Science Foundation ; Freshwater Ecology and Biotechnology Laboratory ; Freshwater Ecology and Biotechnology Laboratory ; Freshwater Ecology and Biotechnology Laboratory ; Freshwater Ecology and Biotechnology Laboratory ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation ; National Natural Science Foundation ; National Natural Science Foundation ; National Natural Science Foundation ; Freshwater Ecology and Biotechnology Laboratory ; Freshwater Ecology and Biotechnology Laboratory ; Freshwater Ecology and Biotechnology Laboratory ; Freshwater Ecology and Biotechnology Laboratory |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.ihb.ac.cn/handle/342005/27785 |
| Collection | 鱼类生物学及渔业生物技术研究中心 |
| Corresponding Author | Zhang, Yi-Bing |
| Affiliation | 1.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Hubei, Peoples R China 2.Univ Chinese Acad Sci, Dept Aquaculture, Wuhan 430072, Hubei, Peoples R China 3.Chinese Acad Sci, Innovat Acad Seed Design, Wuhan 430072, Hubei, Peoples R China 4.Chinese Acad Sci, Inst Hydrobiol, Minist Agr, Key Lab Aquaculture Dis Control, Wuhan 430072, Hubei, Peoples R China |
| Recommended Citation GB/T 7714 | Wu, Min,Zhao, Xiang,Gong, Xiu-Ying,et al. FTRCA1, a Species-Specific Member of finTRIM Family, Negatively Regulates Fish IFN Response through Autophage-Lysosomal Degradation of TBK1[J]. JOURNAL OF IMMUNOLOGY,2019,202(8):2407-2420. |
| APA | Wu, Min,Zhao, Xiang,Gong, Xiu-Ying,Wang, Yang,Gui, Jian-Fang,&Zhang, Yi-Bing.(2019).FTRCA1, a Species-Specific Member of finTRIM Family, Negatively Regulates Fish IFN Response through Autophage-Lysosomal Degradation of TBK1.JOURNAL OF IMMUNOLOGY,202(8),2407-2420. |
| MLA | Wu, Min,et al."FTRCA1, a Species-Specific Member of finTRIM Family, Negatively Regulates Fish IFN Response through Autophage-Lysosomal Degradation of TBK1".JOURNAL OF IMMUNOLOGY 202.8(2019):2407-2420. |
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