FTRCA1, a Species-Specific Member of finTRIM Family, Negatively Regulates Fish IFN Response through Autophage-Lysosomal Degradation of TBK1

doi:10.4049/jimmunol.1801645

	FTRCA1, a Species-Specific Member of finTRIM Family, Negatively Regulates Fish IFN Response through Autophage-Lysosomal Degradation of TBK1
	Wu, Min 1,2; Zhao, Xiang 1,2; Gong, Xiu-Ying 1,2; Wang, Yang 1,2; Gui, Jian-Fang 1,2,3; Zhang, Yi-Bing 1,2,3,4
刊名	JOURNAL OF IMMUNOLOGY
	2019-04-15
卷号	202 期号:8 页码:2407-2420
ISSN号	0022-1767
DOI	10.4049/jimmunol.1801645
通讯作者	Zhang, Yi-Bing(ybzhang@ihb.ac.cn)
英文摘要	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.
资助项目	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关键词	ANTIVIRAL IMMUNE-RESPONSE ; INNATE IMMUNE ; ZEBRAFISH IRF1 ; TRIM FAMILY ; INTERFERON ; EXERTS ; ACTIVATION ; ROLES ; MOTIF ; PROTEINS
WOS研究方向	Immunology
语种	英语
出版者	AMER ASSOC IMMUNOLOGISTS
WOS记录号	WOS:000463861100021
资助机构	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
内容类型	期刊论文
源URL	[http://ir.ihb.ac.cn/handle/342005/27784]
专题	水生生物研究所_鱼类生物学及渔业生物技术研究中心
通讯作者	Zhang, Yi-Bing
作者单位	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
推荐引用方式 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.