1. O-Linked N-Acetylglucosamine Modification of Mitochondrial Antiviral Signaling Protein Regulates Antiviral Signaling by Modulating Its Activity
- Author
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Junghwa Seo, Yun Soo Park, Tae Hyun Kweon, Jingu Kang, Seongjin Son, Han Byeol Kim, Yu Ri Seo, Min Jueng Kang, Eugene C. Yi, Yong-ho Lee, Jin-Hong Kim, Boyoun Park, Won Ho Yang, and Jin Won Cho
- Subjects
0301 basic medicine ,TRAF3 ,lcsh:Immunologic diseases. Allergy ,Immunology ,Host Defense Mechanism ,RIG-I-like receptors signaling ,mitochondrial antiviral signaling protein ,03 medical and health sciences ,0302 clinical medicine ,O-linked N-Acetylglucosamine (O-GlcNAc) ,Transcription (biology) ,Immunology and Allergy ,innate immunity ,Mitochondrial antiviral-signaling protein ,Original Research ,Innate immune system ,biology ,Chemistry ,biology.organism_classification ,Sendai virus ,Cell biology ,030104 developmental biology ,030220 oncology & carcinogenesis ,host defense mechanism ,Signal transduction ,IRF3 ,lcsh:RC581-607 - Abstract
Post-translational modifications, including O-GlcNAcylation, play fundamental roles in modulating cellular events, including transcription, signal transduction, and immune signaling. Several molecular targets of O-GlcNAcylation associated with pathogen-induced innate immune responses have been identified; however, the direct regulatory mechanisms linking O-GlcNAcylation with antiviral RIG-I-like receptor signaling are not fully understood. In this study, we found that cellular levels of O-GlcNAcylation decline in response to infection with Sendai virus. We identified a heavily O-GlcNAcylated serine-rich region between amino acids 249–257 of the mitochondrial antiviral signaling protein (MAVS); modification at this site disrupts MAVS aggregation and prevents MAVS-mediated activation and signaling. O-GlcNAcylation of the serine-rich region of MAVS also suppresses its interaction with TRAF3; this prevents IRF3 activation and production of interferon-β. Taken together, these results suggest that O-GlcNAcylation of MAVS may be a master regulatory event that promotes host defense against RNA viruses.
- Published
- 2021
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