Abstract
After a viral infection and the stimulation of some pattern-recognition receptors as the toll-like receptor 3 in the endosomes or the RIG-I-like receptors in the cytosol, activation of the IKK-related kinase TBK1 leads to the production of type I interferons (IFNs) after phosphorylation of the transcription factors IRF3 and IRF7. Recent findings indicate an involvement of K63-linked polyubiquitination and of the Golgi-localized protein optineurin (OPTN) in the activation of this crucial kinase involved in innate antiviral immunity. This review summarizes the sensing of viruses and the signaling leading to type I IFN production following TBK1 activation through its ubiquitination and the sensing of ubiquitin chains by OPTN at the Golgi apparatus.
Keywords:
Golgi apparatus; TBK1; innate immunity; optineurin; viruses.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Cell Cycle Proteins
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Golgi Apparatus / immunology
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Humans
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Immunity, Innate*
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Interferon Regulatory Factor-3 / immunology
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Interferon Regulatory Factor-3 / metabolism
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Interferon Regulatory Factor-7 / immunology
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Interferon Regulatory Factor-7 / metabolism
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Interferon Type I / immunology
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Interferon Type I / metabolism*
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Membrane Transport Proteins
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Mice
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Phosphorylation
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Protein Serine-Threonine Kinases / immunology
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Protein Serine-Threonine Kinases / metabolism
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Signal Transduction*
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Transcription Factor TFIIIA / genetics
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Transcription Factor TFIIIA / immunology*
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Ubiquitination*
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Virus Diseases / immunology*
Substances
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Cell Cycle Proteins
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IRF7 protein, human
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Interferon Regulatory Factor-3
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Interferon Regulatory Factor-7
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Interferon Type I
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Membrane Transport Proteins
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OPTN protein, human
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Transcription Factor TFIIIA
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Protein Serine-Threonine Kinases
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TBK1 protein, human