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Publication : Multiple functions of the IKK-related kinase IKKepsilon in interferon-mediated antiviral immunity.

First Author  Tenoever BR Year  2007
Journal  Science Volume  315
Issue  5816 Pages  1274-8
PubMed ID  17332413 Mgi Jnum  J:119791
Mgi Id  MGI:3703273 Doi  10.1126/science.1136567
Citation  Tenoever BR, et al. (2007) Multiple functions of the IKK-related kinase IKKepsilon in interferon-mediated antiviral immunity. Science 315(5816):1274-8
abstractText  IKKepsilon is an IKK (inhibitor of nuclear factor kappaBkinase)-related kinase implicated in virus induction of interferon-beta (IFNbeta). We report that, although mice lacking IKKepsilon produce normal amounts of IFNbeta, 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 IKKepsilon because the interferon-stimulated gene factor 3 complex (ISGF3) does not bind to promoter elements of the affected genes. We demonstrate that IKKepsilon is activated by IFNbeta and that IKKepsilon directly phosphorylates signal transducer and activator of transcription 1 (STAT1), a component of ISGF3. We conclude that IKKepsilon plays a critical role in the IFN-inducible antiviral transcriptional response.
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