A role for NF-kappa B in the induction of beta-R1 by interferon-beta.
Previous experiments have suggested that induction of the beta-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 nuclear 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-expression of an IkappaBalpha super-repressor abrogated IFN-beta-mediated induction of a beta-R1 promoter-reporter. IFN-beta treatment did not augment abundance of NF-kappaB but did lead to phosphorylation of the p65 NF-kappaB subunit. It is proposed that IFN-beta-mediated enhancement of the transactivation competence of NF-kappaB components is required for inducible transcription of the beta-R1 promoter. These results provide a novel insight into the role of NF-kappaB in the transcriptional response to IFN-beta.
Rani
M R
MR
Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Asthagiri
A R
AR
Singh
A
A
Sizemore
N
N
Sathe
S S
SS
Li
X
X
DiDonato
J D
JD
Stark
G R
GR
Ransohoff
R M
RM
D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D017930:Genes, Reporter; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016899:Interferon-beta / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D013997:Time Factors; D051996:Transcription Factor RelA; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C494227:IRF9 protein, human; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016328:NF-kappa B; D051996:Transcription Factor RelA; D014157:Transcription Factors; D016899:Interferon-beta