Multiple Functions of the IKK-Related Kinase IKKε in Interferon-Mediated Antiviral Immunity
- 2 March 2007
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 315 (5816) , 1274-1278
- https://doi.org/10.1126/science.1136567
Abstract
IKKϵ is an IKK (inhibitor of nuclear factor κBkinase)–related kinase implicated in virus induction of interferon-β (IFNβ). We report that, although mice lacking IKKϵ produce normal amounts of IFNβ, they are hypersusceptible to viral infection because of a defect in the IFN signaling pathway. Specifically, a subset of type I IFN-stimulated genes are not activated in the absence of IKKϵ because the interferon-stimulated gene factor 3 complex (ISGF3) does not bind to promoter elements of the affected genes. We demonstrate that IKKϵ is activated by IFNβ and that IKKϵ directly phosphorylates signal transducer and activator of transcription 1 (STAT1), a component of ISGF3. We conclude that IKKϵ plays a critical role in the IFN-inducible antiviral transcriptional response.Keywords
This publication has 18 references indexed in Scilit:
- Type 1 Interferons and the Virus-Host Relationship: A Lesson in DétenteScience, 2006
- Mechanisms of type-I- and type-II-interferon-mediated signallingNature Reviews Immunology, 2005
- Structural Bases of Unphosphorylated STAT1 Association and Receptor BindingMolecular Cell, 2005
- Differential Requirement for TANK-binding Kinase-1 in Type I Interferon Responses to Toll-like Receptor Activation and Viral InfectionThe Journal of Experimental Medicine, 2004
- The Roles of Two IκB Kinase-related Kinases in Lipopolysaccharide and Double Stranded RNA Signaling and Viral InfectionThe Journal of Experimental Medicine, 2004
- Triggering the Interferon Antiviral Response Through an IKK-Related PathwayScience, 2003
- IKKε and TBK1 are essential components of the IRF3 signaling pathwayNature Immunology, 2003
- IKK-i, a novel lipopolysaccharide-inducible kinase that is related to IκB kinasesInternational Immunology, 1999
- Virus Infection Induces the Assembly of Coordinately Activated Transcription Factors on the IFN-β Enhancer In VivoMolecular Cell, 1998
- Targeted Disruption of the Mouse Stat1 Gene Results in Compromised Innate Immunity to Viral DiseaseCell, 1996