TY - JOUR
T1 - Multiple functions of the IKK-related kinase IKKε in interferon-mediated antiviral immunity
AU - TenOever, Benjamin R.
AU - Ng, Sze Ling
AU - Chua, Mark A.
AU - McWhirter, Sarah M.
AU - García-Sastre, Adolfo
AU - Maniatis, Tom
PY - 2007/3/2
Y1 - 2007/3/2
N2 - IKKε is an IKK (inhibitor of nuclear factor κB kinase)-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.
AB - IKKε is an IKK (inhibitor of nuclear factor κB kinase)-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.
UR - http://www.scopus.com/inward/record.url?scp=33847687659&partnerID=8YFLogxK
U2 - 10.1126/science.1136567
DO - 10.1126/science.1136567
M3 - Article
C2 - 17332413
AN - SCOPUS:33847687659
SN - 0036-8075
VL - 315
SP - 1274
EP - 1278
JO - Science
JF - Science
IS - 5816
ER -