title: A human aryl hydrocarbon receptor signaling pathway constructed in yeast displays additive responses to ligand mixtures.
abstract: An optimized signal transduction pathway that reproduces the response of human aryl hydrocarbon (Ah) receptor to ligands has been established in Saccharomyces cerevisiae. Ligand treatment induced a 50-fold increase in beta-galactosidase activity from a reporter plasmid in yeast engineered to express human Ah receptor and Ah nuclear translocator (Arnt) proteins. The archetypal Ah receptor ligand, 2,3,7,8-tetrachlorodibenzo(p)dioxin, activated Ah receptor and induced lacZ reporter activity at concentrations of >/=0.3 nM. Mixtures of halogenated and nonhalogenated Ah receptor ligands produced additive signaling responses in this yeast bioassay. These results were consistent with the existence of a common binding site and mechanism of ligand-mediated Ah receptor activation. Although yeast have no natural counterpart to the Ah receptor pathway, expression of human Ah receptor and Arnt under the appropriate conditions provides a functional model system for studying Ah receptor activation and signal transduction.
authors.affiliation: Environmental Health Sciences Department, Tulane University School of Public Health and Tropical Medicine, Tulane-Xavier Center for Bioenvironmental Research, 1430 Tulane Avenue, New Orleans, Louisiana, 70112, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Miller
mesh_terms: D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D001483:Base Sequence; D001564:Benzo(a)pyrene / Q000633:toxicity; D001665:Binding Sites; D004268:DNA-Binding Proteins; D004357:Drug Synergism; D017930:Genes, Reporter; D005818:Genetic Engineering; D006581:Hexachlorobenzene / Q000633:toxicity; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D010957:Plasmids; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism; D019324:beta-Naphthoflavone / Q000633:toxicity
chemical_list: C497396:ARNT protein, human; D004268:DNA-Binding Proteins; D008024:Ligands; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D001564:Benzo(a)pyrene; D006581:Hexachlorobenzene; D019324:beta-Naphthoflavone; D001616:beta-Galactosidase