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学科主题: Immunology
题名: Characterization of Fish IRF3 as an IFN-Inducible Protein Reveals Evolving Regulation of IFN Response in Vertebrates
作者: Sun, Fan1; Zhang, Yi-Bing1; Liu, Ting-Kai1; Gan, Li1; Yu, Fei-Fei1; Liu, Ying1; Gui, Jian-Fang1
通讯作者: Zhang, YB, Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Grad Sch, Wuhan 430072, Peoples R China
关键词: DOUBLE-STRANDED-RNA
刊名: JOURNAL OF IMMUNOLOGY
发表日期: 2010-12-15
DOI: 10.4049/jimmunol.1002401
卷: 185, 期:12, 页:7573-7582
收录类别: SCI
文章类型: Article
部门归属: [Sun, Fan; Zhang, Yi-Bing; Liu, Ting-Kai; Gan, Li; Yu, Fei-Fei; Liu, Ying; Gui, Jian-Fang] Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Grad Sch, Wuhan 430072, Peoples R China
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
资助者: 973 National Basic Research Program of China [2010CB126303]; 863 High Technology Research Program of China [2007AA09Z423]; National Natural Science Foundation of China [30871922]; National Transgenic Project [2009ZX08010-021B]; Freshwater Ecology and Biotechnology Laboratory [2009FBZ01]
类目[WOS]: Immunology
研究领域[WOS]: Immunology
摘要: In mammals, IFN regulatory factor (IRF) 3 is a critical player in modulating transcription of type I IFN and IFN-stimulated genes (ISGs). In this study, we describe the roles of crucian carp (Carassius auratus L.) IRF3 in activating fish IFN and ISGs. Fish IRF3 exhibits a large sequence divergence from mammalian orthologs. Whereas mammalian IRF3 is constitutively expressed, fish IRF3 protein is significantly upregulated by IFN, poly-IC, and other stimuli known as IFN inducers in mammals. The IFN-inducible property of fish IRF3 is consistent with the comparative analysis of 5' flanking regulatory region of vertebrate IRF3 genes, which reveals the presence of typical IFN-stimulated response elements in fish and amphibians, but an absence in tetrapods. Furthermore, either IFN or poly-IC induces phosphorylation and cytoplasmic-to-nuclear translocation of IRF3, which seems essential for its function in that phosphomimic active IRF3 exhibits stronger transactivation than wild type IRF3. Finally, overexpression of fish IRF3 activates production of IFN that in turn triggers ISG transcription through Stat1 pathway, whereas transfection of dominant negative mutant IRF3-DN abrogates poly-IC induction of ISGs, probably owing to blockade of IFN production. Therefore, regulation of IFN response by vertebrate IRF3 is another ancient trait. These data provide evidence of the evolving function of vertebrate IRF3 on regulating IFN response. The Journal of Immunology, 2010, 185: 7573-7582.
英文摘要: In mammals, IFN regulatory factor (IRF) 3 is a critical player in modulating transcription of type I IFN and IFN-stimulated genes (ISGs). In this study, we describe the roles of crucian carp (Carassius auratus L.) IRF3 in activating fish IFN and ISGs. Fish IRF3 exhibits a large sequence divergence from mammalian orthologs. Whereas mammalian IRF3 is constitutively expressed, fish IRF3 protein is significantly upregulated by IFN, poly-IC, and other stimuli known as IFN inducers in mammals. The IFN-inducible property of fish IRF3 is consistent with the comparative analysis of 5' flanking regulatory region of vertebrate IRF3 genes, which reveals the presence of typical IFN-stimulated response elements in fish and amphibians, but an absence in tetrapods. Furthermore, either IFN or poly-IC induces phosphorylation and cytoplasmic-to-nuclear translocation of IRF3, which seems essential for its function in that phosphomimic active IRF3 exhibits stronger transactivation than wild type IRF3. Finally, overexpression of fish IRF3 activates production of IFN that in turn triggers ISG transcription through Stat1 pathway, whereas transfection of dominant negative mutant IRF3-DN abrogates poly-IC induction of ISGs, probably owing to blockade of IFN production. Therefore, regulation of IFN response by vertebrate IRF3 is another ancient trait. These data provide evidence of the evolving function of vertebrate IRF3 on regulating IFN response. The Journal of Immunology, 2010, 185: 7573-7582.
关键词[WOS]: DOUBLE-STRANDED-RNA ; INNATE IMMUNE-RESPONSE ; NF-KAPPA-B ; ATLANTIC SALMON ; PARALICHTHYS-OLIVACEUS ; TRANSCRIPTION FACTORS ; FUNCTIONAL-ANALYSIS ; INDEPENDENT ACTIVATION ; ONCORHYNCHUS-MYKISS ; ANTIVIRAL RESPONSE
语种: 英语
WOS记录号: WOS:000284878700056
ISSN号: 0022-1767
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/13567
Appears in Collections:鱼类生物学及渔业生物技术研究中心_期刊论文

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作者单位: 1.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Grad Sch, Wuhan 430072, Peoples R China

Recommended Citation:
Sun, Fan; Zhang, Yi-Bing; Liu, Ting-Kai; Gan, Li; Yu, Fei-Fei; Liu, Ying; Gui, Jian-Fang.Characterization of Fish IRF3 as an IFN-Inducible Protein Reveals Evolving Regulation of IFN Response in Vertebrates,JOURNAL OF IMMUNOLOGY,2010,185(12):7573-7582
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