title: Regulation of TBK1 activity by Optineurin contributes to cell cycle-dependent expression of the interferon pathway.
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.
authors.affiliation: Institut Pasteur, Signaling and Pathogenesis Laboratory, CNRS UMR 3691, 75724 Paris Cedex 15, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Weil
authors.affiliation: Institut Pasteur, Signaling and Pathogenesis Laboratory, CNRS UMR 3691, 75724 Paris Cedex 15, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Laplantine
authors.affiliation: Institut Pasteur, Signaling and Pathogenesis Laboratory, CNRS UMR 3691, 75724 Paris Cedex 15, France. Electronic address: pierre.genin@pasteur.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Génin
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000276:immunology / Q000473:pathology; D000818:Animals; D001424:Bacterial Infections / Q000276:immunology / Q000473:pathology; D002453:Cell Cycle / Q000276:immunology*; D018797:Cell Cycle Proteins; D005786:Gene Expression Regulation / Q000276:immunology*; D005902:Glaucoma, Open-Angle / Q000276:immunology / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D007372:Interferons / Q000276:immunology*; D026901:Membrane Transport Proteins; D010001:Osteitis Deformans / Q000276:immunology / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000276:immunology*; D035582:Transcription Factor TFIIIA / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology / Q000473:pathology
chemical_list: D018797:Cell Cycle Proteins; D026901:Membrane Transport Proteins; C409460:OPTN protein, human; D035582:Transcription Factor TFIIIA; D007372:Interferons; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human
keywords: Antiviral host defence; Autophagy; Cell cycle regulation; Innate immunity