Zebrafish STAT6 negatively regulates IFN phi 1 production by attenuating the kinase activity of TANK-binding kinase 1 | |
Li, Shun1; Lu, Long-Feng1,2; LaPatra, Scott E.3; Chen, Dan-Dan1; Zhang, Yong-An1 | |
刊名 | DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY |
2017-02-01 | |
卷号 | 67期号:1页码:189-201 |
关键词 | STAT6 Negative regulator Interferon TBK1 Zebrafish |
ISSN号 | 0145-305X |
DOI | 10.1016/j.dci.2016.10.003 |
英文摘要 | The aquatic spring viremia of carp virus (SVCV) causes significant mortality in common carp (Cyprinus carpio), and TBK1 plays a crucial role in the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) system by phosphorylating its substrates to induce type I interferons (IFNs) and cellular antiviral responses. In this study, we report that zebrafish STAT6 is induced during SVCV infection and reduces IFN phi 1 expression by suppressing TBK1 phosphorylation. A typical IFN stimulatory response element (ISRE) motif was found in the promoter region of zebrafish STAT6, and zebrafish STAT6 transcription was significantly upregulated in the early stages of virus infection. Overexpression of STAT6 interfered with IFN phi 1 promoter activity in response to SVCV infection. Additionally, TBK1-, but not MITA-mediated activation of the IFN phi 1 promoter was impaired by STAT6. Co-immunoprecipitation and Western blot experiments indicated that MITA and IRF3 were significantly phosphorylated by TBK1, and that the N-terminal kinase domain of TBK1 was critical in this process. In the final step, STAT6 interacted with the N-terminal kinase domain of TBK1 causing dephosphorylation, which resulted in reductions in the phosphorylation of IRF3 and the production of IFN phi 1. These results indicate that fish STAT6 can attenuate the kinase activity of TBK1, leading to suppression of IFN phi 1 expression which may in turn facilitate virus replication. (C) 2016 Elsevier Ltd. All rights reserved. |
资助项目 | National Basic Research Program of China[2014CB138601] ; National Natural Science Foundation of China[31502200] ; Knowledge Innovation Program of the Chinese Academy of Sciences[Y65E01-1-501] |
WOS关键词 | INNATE IMMUNE-RESPONSE ; I-INTERFERON ; ANTIVIRAL RESPONSE ; FISH ; ACTIVATION ; TRANSCRIPTION ; INDUCTION ; TBK1 ; IRF3 ; CELL |
WOS研究方向 | Immunology ; Zoology |
语种 | 英语 |
出版者 | ELSEVIER SCI LTD |
WOS记录号 | WOS:000390071200018 |
资助机构 | National Basic Research Program of China ; National Basic Research Program of China ; National Basic Research Program of China ; National Basic Research Program of China ; National Basic Research Program of China ; National Basic Research Program of China ; National Basic Research Program of China ; National Basic Research Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Knowledge Innovation Program of the Chinese Academy of Sciences ; Knowledge Innovation Program of the Chinese Academy of Sciences ; Knowledge Innovation Program of the Chinese Academy of Sciences ; Knowledge Innovation Program of the Chinese Academy of Sciences ; Knowledge Innovation Program of the Chinese Academy of Sciences ; 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内容类型 | 期刊论文 |
源URL | [http://ir.ihb.ac.cn/handle/342005/33405] |
专题 | 水生生物研究所_水生生物分子与细胞生物学研究中心_期刊论文 |
通讯作者 | Zhang, Yong-An |
作者单位 | 1.Chinese Acad Sci, State Key Lab Freshwater Ecol & Biotechnol, Inst Hydrobiol, Wuhan 430072, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Clear Spring Foods Inc, Div Res, Buhl, ID 83316 USA |
推荐引用方式 GB/T 7714 | Li, Shun,Lu, Long-Feng,LaPatra, Scott E.,et al. Zebrafish STAT6 negatively regulates IFN phi 1 production by attenuating the kinase activity of TANK-binding kinase 1[J]. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY,2017,67(1):189-201. |
APA | Li, Shun,Lu, Long-Feng,LaPatra, Scott E.,Chen, Dan-Dan,&Zhang, Yong-An.(2017).Zebrafish STAT6 negatively regulates IFN phi 1 production by attenuating the kinase activity of TANK-binding kinase 1.DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY,67(1),189-201. |
MLA | Li, Shun,et al."Zebrafish STAT6 negatively regulates IFN phi 1 production by attenuating the kinase activity of TANK-binding kinase 1".DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 67.1(2017):189-201. |
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