NK-kappa B subunit-specific regulation of the I kappa B alpha promoter.
Stimulation of endothelial cells by cytokines and bacterial lipopolysaccharide leads to activation of the transcription factor NF-kappa B. NF-kappa B in turn regulates the expression of several genes involved in the inflammatory reaction, including cell adhesion molecules, interleukins, and transcription factors. One of these induced genes encodes an inhibitor of NF-kappa B, ECI-6/I kappa B alpha, that contains in its 5' regulatory region six consensus binding sites for NF-kappa B. We demonstrate here that these sites display striking differences in their ability in vitro to bind to various NF-kappa B subunits. In vivo, all six sites contribute, though to varying degrees, to transcription from the ECI-6/I kappa B alpha promoter, as demonstrated by deletion and mutation analysis. Among the NF-kappa B subunits tested p65, the p65/p50 heterodimer and, to a lesser extent, c-Rel, are able to activate transcription, whereas p50 or p50/Re1B were inactive. Since many genes regulated by NF-kappa B contain only one or two DNA-binding sites for this transcription factor, the presence of six functional NF-kappa B-binding sites in the ECI-6/I kappa B alpha promoter represents a unique feature of this gene.
Cheng
Q
Q
Vienna International Research Cooperation Center, Austria.
Cant
C A
CA
Moll
T
T
Hofer-Warbinek
R
R
Wagner
E
E
Birnstiel
M L
ML
Bach
F H
FH
de Martin
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020569:Proto-Oncogene Proteins c-rel; D017384:Sequence Deletion; D013552:Swine; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D000072000:NF-KappaB Inhibitor alpha