Regulation of TBK1 activity by Optineurin contributes to cell cycle-dependent expression of the interferon pathway |
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| Institution: | 1. Department of Neurology, Peking University Third Hospital, Beijing, China;2. Beijing Municipal Key Laboratory of Biomarker and Translational Research in Neurodegenerative diseases, Beijing, China;3. Key Laboratory for Neuroscience, National Health Commission/Ministry of Education, Peking University, Beijing, China;1. Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA;2. Department of Cellular & Molecular Physiology, Systems Biology Institute, Yale University School of Medicine, New Haven, CT 06520, USA;1. Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, United States;2. Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, United States;3. Texas Children''s Hospital, Houston, TX 77030, United States;1. Department of Virology, Division of Medicine, Imperial College London, Norfolk Place, London W2 1 PG, UK;2. St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA;3. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France;4. University of Paris Descartes, Imagine Institute, Paris, France;5. Howard Hughes Medical Institute, New York, NY, USA;6. Pediatric Hematology and Immunology Unit, Necker Hospital for Sick Children, Paris, France;7. Department of Pediatrics, Division of Medicine, Imperial College London, Norfolk Place, London W2 1 PG, UK;1. Laboratory of Molecular Immunology, Department of Biotechnology, University of Rijeka, 51000 Rijeka, Croatia;2. Division of Rheumatology, Johns Hopkins School of Medicine, Baltimore, MD 21224, USA;3. Department of Psychiatry and Neuroscience, Faculty of Medicine, Research Centre of the Mental Health Institute of Quebec, Laval University, Quebec, Quebec G1J 2G3, Canada;4. Department of Biotechnology, Jo?ef Stefan Institute, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Biomedical Research Institute BRIS, SI-1000 Ljubljana, Slovenia |
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| Abstract: | The innate immune system has evolved to detect and neutralize viral invasions. Triggering of this defense mechanism relies on the production and secretion of soluble factors that stimulate intracellular antiviral defense mechanisms. The Tank Binding Kinase 1 (TBK1) is a serine/threonine kinase in the innate immune signaling pathways including the antiviral response and the host defense against cytosolic infection by bacteries. Given the critical roles of TBK1, important regulatory mechanisms are required to regulate its activity. Among these, Optineurin (Optn) was shown to negatively regulate the interferon response, in addition to its important role in membrane trafficking, protein secretion, autophagy and cell division. As Optn does not carry any enzymatic activity, its functions depend on its precise subcellular localization and its interaction with other proteins, especially with components of the innate immune pathway. This review highlights advances in our understanding of Optn mechanisms of action with focus on the relationships between Optn and TBK1 and their implication in host defense against pathogens. Specifically, how the antiviral immune system is controlled during the cell cycle by the Optn/TBK1 axis and the physiological consequences of this regulatory mechanism are described. This review may serve to a better understanding of the relationships between the different functions of Optn, including those related to immune responses and its associated pathologies such as primary open-angle glaucoma, amyotrophic lateral sclerosis and Paget’s disease of bone. |
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| Keywords: | Antiviral host defence Innate immunity Cell cycle regulation Autophagy |
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