The involvement of NF-kappa B in beta-interferon gene regulation reveals its role as widely inducible mediator of signal transduction.
The DNA binding protein NF-kappa B has been implicated in gene regulation in B and T lymphocytes. We have found that NF-kappa B also has a central role in virus induction of human beta-interferon (beta-IFN) gene expression. A critical virus-inducible element of this gene, PRDII, behaves interchangeably with the NF-kappa B binding site from the Ig kappa enhancer in both B lymphocytes and virus-infected fibroblasts. Single base substitutions that impair inducibility of the beta-IFN gene in vivo also reduce the binding of NF-kappa B to PRDII in vitro. Virus infection potently activates the binding and nuclear localization of NF-kappa B and, in pre-B lymphocytes, results in the expression of both the beta-IFN gene and the Ig kappa gene. The wide variety of cell types in which beta-interferon can be induced and the divergent set of gene induction processes involving NF-kappa B suggest that this transcription factor plays a broad role in gene regulation as a mediator of inducible signal transduction.
Lenardo
M J
MJ
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142.
Fan
C M
CM
Maniatis
T
T
Baltimore
D
D
D001665:Binding Sites; D001667:Binding, Competitive; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D007075:Immunoglobulin M / Q000235:genetics / Q000378:metabolism; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000378:metabolism; D007370:Interferon Type I / Q000235:genetics*; D016328:NF-kappa B; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D007370:Interferon Type I; D016328:NF-kappa B; D014157:Transcription Factors