Inhibitor of κB kinase is required to activate a subset of interferon γ-stimulated genes

Abstract

IκB kinase (IKK), discovered as the major activator of NF-κB, plays additional roles in signaling. By using mouse embryo fibroblasts (MEFs) lacking both the α and β subunits of IKK, we find that these proteins are required for induction of a major subset of IFNγ-stimulated genes and that this requirement is independent of NF-κB activation. Furthermore, there is no defect in IFNγ-stimulated signal transducer and activator of transcription 1 (Stat1) activation or function in the IKKα/β-null MEFs. Therefore, although activated Stat1 dimers are necessary for the activation of these genes in response to IFNγ, they are not sufficient. These results reveal an important additional pathway for IFNγ-stimulated gene expression in which an NF-κB-independent function of IKK is required.