Multiple Functions of the IKK-Related Kinase IKK
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*
IKK
is an IKK (inhibitor of nuclear factor 
Bkinase)–related kinase implicated in virus induction of interferon-ß (IFNß). We report that, although mice lacking IKK produce normal amounts of IFNß, 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 because the interferon-stimulated gene factor 3 complex (ISGF3) does not bind to promoter elements of the affected genes. We demonstrate that IKK is activated by IFNß and that IKK directly phosphorylates signal transducer and activator of transcription 1 (STAT1), a component of ISGF3. We conclude that IKK 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
