A role for NF-kappa B in the induction of beta-R1 by interferon-beta

Previous experiments have suggested that induction of the beta3-R1 gene by interferon (IFN)-beta required transcription factor ISGF-3 (IFN-stimulated gene factor-3) and an additional component. We now provide evidence that nu clear factor-kappaB (NF-kappaB) can serve as this component. Site-directed mutagenesis of an NF-kappaB binding site in the beta -R1 promoter or over-e xpression of an I kappaB alpha super-repressor abrogated IFN-beta -mediated induction of a beta -R1 promoter-reporter. IFN-beta treatment did not augm ent abundance of NF-kappaB but did lead to phosphorylation of the p65 NF-ka ppaB subunit. It is proposed that IFN-beta -mediated enhancement of the tra nsactivation competence of NF-kappaB components is required for inducible t ranscription of the beta -R1 promoter. These results provide a novel insigh t into the role of NF-kappaB in the transcriptional response to IFN-beta.