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. |
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| 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] |
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| Database: | Engineering Source |
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