Dioxin-inducible transactivation in a chromosomal setting. Analysis of the acidic domain of the Ah receptor.
We analyzed the transactivation function of the acidic segment of the Ah receptor (amino acids 515-583) by reconstituting AhR-defective mouse hepatoma cells with mutants. Our data reveal that both hydrophobic and acidic residues are important for transactivation and that these residues are clustered in two regions of the acidic segment of AhR. Both regions are crucial for function, because disruption of either one substantially impairs transactivation of the chromosomal CYP1A1 target gene. Neither region contains an amino acid motif that resembles those reported for other acidic activation domains. Furthermore, proline substitutions in both regions do not impair transactivation in vivo, a finding that implies that alpha-helix formation is not required for function.
Jones
L C
LC
Division of Hematology and Oncology, Cedars Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA 90048, USA.
Whitlock
J P
JP
D019943:Amino Acid Substitution; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002875:Chromosomes; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D004147:Dioxins / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism; D051379:Mice; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D017433:Protein Structure, Secondary; D018336:Receptors, Aryl Hydrocarbon / Q000737:chemistry* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D004147:Dioxins; D010446:Peptide Fragments; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011993:Recombinant Fusion Proteins; D019363:Cytochrome P-450 CYP1A1