OTUB1 Is a Key Regulator of RIG-I-Dependent Immune Signaling and Is Targeted for Proteasomal Degradation by Influenza A NS1
| العنوان: | OTUB1 Is a Key Regulator of RIG-I-Dependent Immune Signaling and Is Targeted for Proteasomal Degradation by Influenza A NS1 |
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| المؤلفون: | Qi Wen Teo, Adolfo García-Sastre, Leo L.M. Poon, Ho Him Wong, Caroline Demeret, Agathe Le Quang, Artejan te Velthuis, Akhee Sabiha Jahan, Elise Biquand, Alex W.H. Chin, Sumana Sanyal, Sophie A. Valkenburg, Chris Ka Pun Mok, Raquel Muñoz-Moreno |
| المساهمون: | Centre de recherche Université de Hong-Kong-Pasteur, Réseau International des Instituts Pasteur (RIIP), LKS Faculty of Medicine (HKU Med), The University of Hong Kong (HKU), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Addenbrooke's Hospital, Cambridge University NHS Trust, This work was funded by Research Grants Council (GRF) grants 17113915 and 17112617 and partially supported by Health and Medical ResearchFunds (16150592), a theme-based research grant from the ResearchGrants Council (project T11-705/14N), and PTR (546) from Institut Pasteur.S.S. is supported by the Croucher Foundation., Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], te Velthuis, Arend [0000-0002-5129-3953], Apollo - University of Cambridge Repository |
| المصدر: | Cell Reports, Vol 30, Iss 5, Pp 1570-1584.e6 (2020) Cell Reports Cell Reports, Elsevier Inc, 2020, 30 (5), pp.1570-1584.e6. ⟨10.1016/j.celrep.2020.01.015⟩ Cell Reports, 2020, 30 (5), pp.1570-1584.e6. ⟨10.1016/j.celrep.2020.01.015⟩ |
| بيانات النشر: | Elsevier, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Viral pathogenesis, viruses, Regulator, Viral Nonstructural Proteins, Madin Darby Canine Kidney Cells, Cytosol, 0302 clinical medicine, Ubiquitin, Interferon, Receptors, Immunologic, influenza A, lcsh:QH301-705.5, Deubiquitinating Enzymes, biology, Chemistry, RIG-I, deubiquitylases, NF-kappa B, virus diseases, 3. Good health, Cell biology, Cysteine Endopeptidases, OTUB1, Interferon Type I, Mitochondrial Membranes, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, DEAD Box Protein 58, Signal transduction, Signal Transduction, medicine.drug, Proteasome Endopeptidase Complex, RNA virus, chemical and pharmacologic phenomena, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Dogs, Influenza, Human, medicine, Animals, Humans, ubiquitylation, biochemical phenomena, metabolism, and nutrition, viral subversion strategies, HEK293 Cells, 030104 developmental biology, lcsh:Biology (General), A549 Cells, Proteolysis, biology.protein, innate immune response, Interferon Regulatory Factor-3, Protein Multimerization, RIG-I signaling, IRF3, Gene Deletion, 030217 neurology & neurosurgery |
| الوصف: | Summary: Deubiquitylases (DUBs) regulate critical signaling pathways at the intersection of host immunity and viral pathogenesis. Although RIG-I activation is heavily dependent on ubiquitylation, systematic analyses of DUBs that regulate this pathway have not been performed. Using a ubiquitin C-terminal electrophile, we profile DUBs that function during influenza A virus (IAV) infection and isolate OTUB1 as a key regulator of RIG-I-dependent antiviral responses. Upon infection, OTUB1 relocalizes from the nucleus to mitochondrial membranes together with RIG-I, viral PB2, and NS1. Its expression depends on competing effects of interferon stimulation and IAV-triggered degradation. OTUB1 activates RIG-I via a dual mechanism of K48 polyubiquitin hydrolysis and formation of an E2-repressive complex with UBCH5c. We reconstitute this mechanism in a cell-free system comprising [35S]IRF3, purified RIG-I, mitochondrial membranes, and cytosol expressing OTUB1 variants. A range of IAV NS1 proteins trigger proteasomal degradation of OTUB1, antagonizing the RIG-I signaling cascade and antiviral responses. : Jahan et al. describe the role of Otub1, a deubiquitylase that is induced during virus infection in an interferon-dependent manner to regulate optimal signaling via the RIG-I pathway. Influenza A virus NS1 is able to bind and degrade newly synthesized Otub1 as a means to evade the innate immune response. Keywords: deubiquitylases, RIG-I signaling, ubiquitylation, innate immune response, RNA virus, influenza A, viral subversion strategies |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2211-1247 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7749df9e39d91346d4bcd3b64399959aTest http://www.sciencedirect.com/science/article/pii/S2211124720300243Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7749df9e39d91346d4bcd3b64399959a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22111247 |
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