TanK-Binding Kinase 1 (TBK1) Isoforms Negatively Regulate Type I Interferon Induction by Inhibiting TBK1-IRF3 Interaction and IRF3 Phosphorylation

doi:10.3389/fimmu.2018.00084

CORC > 武汉植物园 > 中国科学院武汉植物园

	TanK-Binding Kinase 1 (TBK1) Isoforms Negatively Regulate Type I Interferon Induction by Inhibiting TBK1-IRF3 Interaction and IRF3 Phosphorylation
	Cao, Lu 1; Hu, Yi Wei 1,2; Zhang, Jie 1; Wu, Xiao Man 1; Nie, Pin 1,3; Chang, Ming Xian 1,3
刊名	FRONTIERS IN IMMUNOLOGY
	2018-01-30
卷号	9 页码:17
关键词	alternative splicing spring viremia of carp virus TANK-binding kinase 1 spliced isoforms TANK-binding kinase 1 IRF3 type I interferon signaling immune homeostasis
ISSN号	1664-3224
DOI	10.3389/fimmu.2018.00084
英文摘要	TANK-binding kinase 1 (TBK1) is an important serine/threonine-protein kinase that mediates phosphorylation and nuclear translocation of IRF3, which contributes to induction of type I interferons (IFNs) in the innate antiviral response. In mammals, TBK1 spliced isoform negatively regulates the virus-triggered IFN-beta signaling pathway by disrupting the interaction between retinoic acid-inducible gene I (RIG-I) and mitochondria antiviral-signaling protein (MAVS). However, it is still unclear whether alternative splicing patterns and the function of TBK1 isoform(s) exist in teleost fish. In this study, we identify two alternatively spliced isoforms of TBK1 from zebrafish, termed TBK1_tv1 and TBK1_tv2. Both TBK1_tv1 and TBK1_tv2 contain an incomplete STKc_TBK1 domain. Moreover, the UBL_TBK1_like domain is also missing for TBK1_tv2. TBK1_tv1 and TBK1_tv2 are expressed in zebrafish larvae. Overexpression of TBK1_tv1 and TBK1_tv2 inhibits RIG-I-, MAVS-, TBK1-, and IRF3-mediated activation of IFN promoters in response to spring viremia of carp virus infection. Also, TBK1_tv1 and TBK1_tv2 inhibit expression of IFNs and IFN-stimulated genes induced by MAVS and TBK1. Mechanistically, TBK1_tv1 and TBK1_tv2 competitively associate with TBK1 and IRF3 to disrupt the formation of a functional TBK1-IRF3 complex, impeding the phosphorylation of IRF3 mediated by TBK1. Collectively, these results demonstrate that TBK1 spliced isoforms are dominant negative regulators in the RIG-I/MAVS/TBK1/IRF3 antiviral pathway by targeting the functional TBK1-IRF3 complex formation. Identification and functional characterization of piscine TBK1 spliced isoforms may contribute to understanding the role of TBK1 expression in innate antiviral response.
资助项目	National Natural Science Foundation of China[31372531] ; National Natural Science Foundation of China[31672687]
WOS研究方向	Immunology
语种	英语
出版者	FRONTIERS MEDIA SA
WOS记录号	WOS:000423556800001
内容类型	期刊论文
源URL	[http://202.127.146.157/handle/2RYDP1HH/4620]
专题	中国科学院武汉植物园
通讯作者	Chang, Ming Xian
作者单位	1.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan, Hubei, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Minist Agr, Key Lab Aquaculture Dis Control, Wuhan, Hubei, Peoples R China
推荐引用方式 GB/T 7714	Cao, Lu,Hu, Yi Wei,Zhang, Jie,et al. TanK-Binding Kinase 1 (TBK1) Isoforms Negatively Regulate Type I Interferon Induction by Inhibiting TBK1-IRF3 Interaction and IRF3 Phosphorylation[J]. FRONTIERS IN IMMUNOLOGY,2018,9:17.
APA	Cao, Lu,Hu, Yi Wei,Zhang, Jie,Wu, Xiao Man,Nie, Pin,&Chang, Ming Xian.(2018).TanK-Binding Kinase 1 (TBK1) Isoforms Negatively Regulate Type I Interferon Induction by Inhibiting TBK1-IRF3 Interaction and IRF3 Phosphorylation.FRONTIERS IN IMMUNOLOGY,9,17.
MLA	Cao, Lu,et al."TanK-Binding Kinase 1 (TBK1) Isoforms Negatively Regulate Type I Interferon Induction by Inhibiting TBK1-IRF3 Interaction and IRF3 Phosphorylation".FRONTIERS IN IMMUNOLOGY 9(2018):17.