Abstract
Rapid induction of type I interferon expression, a central event in establishing the innate antiviral response, requires cooperative activation of numerous transcription factors. Although signaling pathways that activate the transcription factors nuclear factor kappaB and ATF-2/c-Jun have been well characterized, activation of the interferon regulatory factors IRF-3 and IRF-7 has remained a critical missing link in understanding interferon signaling. We report here that the IkappaB kinase (IKK)-related kinases IKKepsilon and TANK-binding kinase 1 are components of the virus-activated kinase that phosphorylate IRF-3 and IRF-7. These studies illustrate an essential role for an IKK-related kinase pathway in triggering the host antiviral response to viral infection.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line
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DNA-Binding Proteins / metabolism
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Enzyme Activation
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Gene Expression Regulation, Viral
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Hepacivirus / immunology
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Hepacivirus / physiology*
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Humans
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I-kappa B Kinase
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Interferon Regulatory Factor-3
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Interferon Regulatory Factor-7
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Interferon Type I / biosynthesis*
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Interferon Type I / genetics
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Phosphorylation
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Promoter Regions, Genetic
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Protein Serine-Threonine Kinases / metabolism*
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RNA, Small Interfering / metabolism
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Transcription Factors / metabolism
Substances
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DNA-Binding Proteins
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IRF3 protein, human
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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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RNA, Small Interfering
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Transcription Factors
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Protein Serine-Threonine Kinases
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TBK1 protein, human
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CHUK protein, human
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I-kappa B Kinase
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IKBKB protein, human
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IKBKE protein, human