Negative Feedback Regulation of RIG-I-Mediated Antiviral Signaling by Interferon-Induced ISG15 Conjugation
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- Min-Jung Kim
- Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang 790-784, Republic of Korea
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- Sun-Young Hwang
- Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang 790-784, Republic of Korea
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- Tadaatsu Imaizumi
- Department of Vascular Biology, Hirosaki University School of Medicine, Hirosaki 036-8562, Japan
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- Joo-Yeon Yoo
- Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang 790-784, Republic of Korea
書誌事項
- 公開日
- 2008-02
- 権利情報
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- https://journals.asm.org/non-commercial-tdm-license
- DOI
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- 10.1128/jvi.01650-07
- 公開者
- American Society for Microbiology
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説明
<jats:title>ABSTRACT</jats:title> <jats:p> RIG-I senses intracellular virus-specific nucleic acid structures and initiates an antiviral response that induces interferon (IFN) production, which, in turn, activates the transcription of RIG-I to increase RIG-I protein levels. Upon intracellular poly(I:C) stimulation, however, the levels of RIG-I protein did not correlate with the expression patterns of <jats:italic>RIG-I</jats:italic> transcripts. When the ISG15 conjugation system was overexpressed, ISG15 was conjugated to RIG-I and cellular levels of the unconjugated form of RIG-I decreased. The ISGylation of RIG-I reduced levels of both basal and virus-induced IFN promoter activity. Levels of unconjugated RIG-I also decreased when 26S proteasome activity was blocked by treatment with MG132, ALLN, or Lactacystin. In the presence of MG132, ISG15 conjugation to RIG-I increased, and hence, the unconjugated form of RIG-I was reduced. In Ube1L <jats:sup>−/−</jats:sup> cells, which lack the ability to conjugate ISG15, basal levels of both RIG-I protein and transcripts were increased compared to those in wild-type cells. As a result, enhanced production of ISGs and enhanced IFN promoter activity in Ube1L <jats:sup>−/−</jats:sup> cells were observed, and the phenotype was restored to that of wild-type cells by the overexpression of Ube1L. Based on these results, we propose a novel negative feedback loop which adjusts the strength of the RIG-I-mediated antiviral response and IFN production through the regulation of RIG-I protein by IFN-induced ISG15 conjugation. </jats:p>
収録刊行物
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- Journal of Virology
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Journal of Virology 82 (3), 1474-1483, 2008-02
American Society for Microbiology
