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Negative Regulation of Melanoma Differentiation-associated Gene 5 (MDA5)-dependent Antiviral Innate Immune Responses by Arf-like Protein 5B.

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Title: Negative Regulation of Melanoma Differentiation-associated Gene 5 (MDA5)-dependent Antiviral Innate Immune Responses by Arf-like Protein 5B.
Authors: Yuichi Kitai1,2,3, Osamu Takeuchi4, Takumi Kawasaki1, Daisuke Ori4, Takuya Sueyoshi1, Motoya Murase1, Shizuo Akira2,3, Taro Kawai1 tarokawai@bs.naist.jp
Source: Journal of Biological Chemistry. 1/9/2015, Vol. 290 Issue 2, p1269-1280. 12p.
Subjects: Natural immunity, ADP-ribosylation factors, Ras proteins, Type I interferons, Cytokines, Genetics
Abstract: RIG-I-like receptors (RLRs), including retinoic acid-inducible gene-I (RIG-I) and MDA5, constitute a family of cytoplasmic RNA helicases that senses viral RNA and mounts antiviral innate immunity by producing type I interferons and inflammatory cytokines. Despite their essential roles in antiviral host defense, RLR signaling is negatively regulated to protect the host from excessive inflammation and autoimmunity. Here, we identified ADP-ribosylation factor-like protein 5B (Arl5B), an Arl family small GTPase, as a regulator of RLR signaling through MDA5 but not RIG-I. Overexpression of Arl5B repressed interferon β promoter activation by MDA5 but not RIG-I, and its knockdown enhanced MDA5-mediated responses. Furthermore, Arl5B-deficient mouse embryonic fibroblast cells exhibited increased type I interferon expression in response to MDA5 agonists such as poly(I:C) and encephalomyocarditis virus. Arl5B-mediated negative regulation of MDA5 signaling does not require its GTP binding ability but requires Arl5B binding to the C-terminal domain of MDA5, which prevents interaction between MDA5 and poly(I:C). Our results, therefore, suggest that Arl5B is a negative regulator for MDA5. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Negative Regulation of Melanoma Differentiation-associated Gene 5 (MDA5)-dependent Antiviral Innate Immune Responses by Arf-like Protein 5B.
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  Data: <searchLink fieldCode="AR" term="%22Yuichi+Kitai%22">Yuichi Kitai</searchLink><relatesTo>1,2,3</relatesTo><br /><searchLink fieldCode="AR" term="%22Osamu+Takeuchi%22">Osamu Takeuchi</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Takumi+Kawasaki%22">Takumi Kawasaki</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Daisuke+Ori%22">Daisuke Ori</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Takuya+Sueyoshi%22">Takuya Sueyoshi</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Motoya+Murase%22">Motoya Murase</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Shizuo+Akira%22">Shizuo Akira</searchLink><relatesTo>2,3</relatesTo><br /><searchLink fieldCode="AR" term="%22Taro+Kawai%22">Taro Kawai</searchLink><relatesTo>1</relatesTo><i> tarokawai@bs.naist.jp</i>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+Biological+Chemistry%22">Journal of Biological Chemistry</searchLink>. 1/9/2015, Vol. 290 Issue 2, p1269-1280. 12p.
– Name: Subject
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  Data: <searchLink fieldCode="DE" term="%22Natural+immunity%22">Natural immunity</searchLink><br /><searchLink fieldCode="DE" term="%22ADP-ribosylation+factors%22">ADP-ribosylation factors</searchLink><br /><searchLink fieldCode="DE" term="%22Ras+proteins%22">Ras proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Type+I+interferons%22">Type I interferons</searchLink><br /><searchLink fieldCode="DE" term="%22Cytokines%22">Cytokines</searchLink><br /><searchLink fieldCode="DE" term="%22Genetics%22">Genetics</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: RIG-I-like receptors (RLRs), including retinoic acid-inducible gene-I (RIG-I) and MDA5, constitute a family of cytoplasmic RNA helicases that senses viral RNA and mounts antiviral innate immunity by producing type I interferons and inflammatory cytokines. Despite their essential roles in antiviral host defense, RLR signaling is negatively regulated to protect the host from excessive inflammation and autoimmunity. Here, we identified ADP-ribosylation factor-like protein 5B (Arl5B), an Arl family small GTPase, as a regulator of RLR signaling through MDA5 but not RIG-I. Overexpression of Arl5B repressed interferon β promoter activation by MDA5 but not RIG-I, and its knockdown enhanced MDA5-mediated responses. Furthermore, Arl5B-deficient mouse embryonic fibroblast cells exhibited increased type I interferon expression in response to MDA5 agonists such as poly(I:C) and encephalomyocarditis virus. Arl5B-mediated negative regulation of MDA5 signaling does not require its GTP binding ability but requires Arl5B binding to the C-terminal domain of MDA5, which prevents interaction between MDA5 and poly(I:C). Our results, therefore, suggest that Arl5B is a negative regulator for MDA5. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1074/jbc.M114.611053
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        Text: English
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      – SubjectFull: Natural immunity
        Type: general
      – SubjectFull: ADP-ribosylation factors
        Type: general
      – SubjectFull: Ras proteins
        Type: general
      – SubjectFull: Type I interferons
        Type: general
      – SubjectFull: Cytokines
        Type: general
      – SubjectFull: Genetics
        Type: general
    Titles:
      – TitleFull: Negative Regulation of Melanoma Differentiation-associated Gene 5 (MDA5)-dependent Antiviral Innate Immune Responses by Arf-like Protein 5B.
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            NameFull: Yuichi Kitai
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            – D: 09
              M: 01
              Text: 1/9/2015
              Type: published
              Y: 2015
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              Value: 290
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