Transcriptional activation by the mouse Ah receptor. Interplay between multiple stimulatory and inhibitory functions.
The aromatic hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that mediates cellular responses to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We cloned AhR cDNA from C57BL/6 mouse liver and verified by transfection that it encodes a functional protein. Analyses of deletion mutants indicate that the carboxyl half of AhR contains several types of transactivation domain, which function independently of domains that mediate TCDD recognition, DNA binding, and heterodimerization with the Ah receptor nuclear translocator (Arnt) protein. The transactivation domains function independently of each other, display different levels of activity, and act synergistically when linked. In addition, AhR contains an 82-amino acid domain that inhibits transactivation. The inhibitory domain displays specificity, in that it blocks the transactivating functions of AhR and Arnt, but not that of the herpes simplex protein VP16. The inhibitory activity depends upon the cell type in which AhR is expressed, implying that a cell-specific protein mediates the effect.
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Department of Molecular Pharmacology, Stanford University School of Medicine, California 94305-5332, USA.
Dong
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Whitlock
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JP
D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D017405:Herpes Simplex Virus Protein Vmw65 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction / Q000235:genetics; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation
C497397:Arnt protein, mouse; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D017405:Herpes Simplex Virus Protein Vmw65; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator