Superinduction of CYP1A1 transcription by cycloheximide. Role of the DNA binding site for the liganded Ah receptor.
Nuclear run-off experiments reveal that four distinct DNA domains, each of which contains a binding site for the liganded Ah receptor, can mediate the superinduction of transcription by 2,3,7,8-tetrachlorodibenzo-p-dioxin plus cycloheximide. Superinduction requires substantial inhibition of protein synthesis by cycloheximide. Gel retardation analyses of nuclear extracts and methylation protection studies in intact cells reveal no evidence for cycloheximide-sensitive protein-DNA interactions that might mediate the superinduction response. These observations suggest the existence of a labile protein(s) that acts to inhibit the function of the dioxin-responsive receptor/enhancer regulatory system via protein-protein interactions.
Lusska
A
A
Department of Pharmacology, Stanford University School of Medicine, California 94305.
Wu
L
L
Whitlock
J P
JP
D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D008969:Molecular Sequence Data; D010957:Plasmids; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection
D004268:DNA-Binding Proteins; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; D004247:DNA; D003513:Cycloheximide