Tumor necrosis factor beta (TNF-beta) induces binding of the NF-kappa B transcription factor to a high-affinity kappa B element in the TNF-beta promoter.
The expression of the gene encoding tumor necrosis factor beta (TNF-beta) (lymphotoxin) is induced in T cells by various extracellular stimuli. We noticed that most such stimuli also activate the NF-kappa B transcription factor. Here we demonstrate binding of purified human NF-kappa B to a sequence within positions -98 to -88 (5'-GGGGCTTCCCC-3') of the TNF-beta promoter, which is conserved between the human and mouse genes. Also the NF-kappa B from the human T-cell line Jurkat, activated upon phytohemagglutinin (PHA)/phorbol 12-myristate 13-acetate (PMA/TPA) treatment in vivo or upon deoxycholate treatment in vitro, binds with high affinity to the sequence in the TNF-beta promoter. Apart from a single mismatch, the site is identical to a cis-activating element that is involved in the inducible expression of the MHC class I gene H-2Kb and which interacts with both the inducible NF-kappa B transcription factor and the constitutive factor KBF1/H2TF1, as we demonstrate here for the site in the TNF-beta promoter. The high homology of the well characterized H-2Kb enhancer sequence with the TNF-beta site with regard to sequence and factor binding strongly supports a physiological role for NF-kappa B in the inducible expression of the TNF-beta gene. Our observation that the TNF-beta protein can rapidly induce the DNA-binding activity of NF-kappa B in Jurkat T cells and transiently increase TNF-beta mRNA levels suggests that NF-kappa B can mediate a positive autoregulation of TNF-beta synthesis.
Messer
G
G
Institute of Immunology, Ludwigs-Maximilians-University, Munich, Germany.
Weiss
E H
EH
Baeuerle
P A
PA
D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D003840:Deoxycholic Acid / Q000494:pharmacology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008233:Lymphotoxin-alpha / Q000235:genetics* / Q000494:pharmacology; D008745:Methylation; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012689:Sequence Homology, Nucleic Acid; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D008233:Lymphotoxin-alpha; D016328:NF-kappa B; D003840:Deoxycholic Acid; D013755:Tetradecanoylphorbol Acetate