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Science 315 (5816): 1274-1278

Copyright © 2007 by the American Association for the Advancement of Science

Multiple Functions of the IKK-Related Kinase IKK{varepsilon} in Interferon-Mediated Antiviral Immunity

Benjamin R. tenOever,1 Sze-Ling Ng,1 Mark A. Chua,2,3 Sarah M. McWhirter,1 Adolfo García-Sastre,2,4 Tom Maniatis1*

Abstract: IKK{epsilon} is an IKK (inhibitor of nuclear factor {kappa}Bkinase)–related kinase implicated in virus induction of interferon-β (IFNβ). We report that, although mice lacking IKK{epsilon} 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 IKK{epsilon} because the interferon-stimulated gene factor 3 complex (ISGF3) does not bind to promoter elements of the affected genes. We demonstrate that IKK{epsilon} is activated by IFNβ and that IKK{epsilon} directly phosphorylates signal transducer and activator of transcription 1 (STAT1), a component of ISGF3. We conclude that IKK{epsilon} plays a critical role in the IFN-inducible antiviral transcriptional response.

1 Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA02138, USA.
2 Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA.
3 Microbiology Graduate School Training Program, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA.
4 Emerging Pathogens Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA.

* To whom correspondence should be addressed. E-mail: maniatis{at}mcb.harvard.edu


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