Cloning of a Factor Required for Activity of the Ah (Dioxin) Receptor

• Published in: Science (American Association for the Advancement of Science) Vol. 252; no. 5008; pp. 954 - 958
• Main Authors: Hoffman, Emily C., Reyes, Herminio, Chu, Fong-Fong, Sander, Fred, Conley, Linda H., Brooks, Barbara A., Hankinson, Oliver
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 17.05.1991; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: 560300 - Chemicals Metabolism & Toxicology; Ah receptor-binding protein; AMINES; Amino Acid Sequence; Amino acids; AROMATICS; Aryl Hydrocarbon Receptor Nuclear Translocator; Aryl hydrocarbon receptors; aryl hydrocarbons; Base Sequence; BIOCHEMICAL REACTION KINETICS; Biological and medical sciences; Cell Line; Cell lines; Cell Nucleus - metabolism; Cell receptors; Cell structures and functions; CHLORINATED AROMATIC HYDROCARBONS; CLONING; Cloning, Molecular; Complementary DNA; COS cells; Cytosol - metabolism; Deoxyribonucleic acid; Dioxin; Dioxins; DNA; DNA binding proteins; DNA HYBRIDIZATION; DNA-CLONING; Exons; Fundamental and applied biological sciences. Psychology; GENES; Genetics; HALOGENATED AROMATIC HYDROCARBONS; Hep G2 cells; HETEROCYCLIC COMPOUNDS; Humans; HYBRIDIZATION; HYDROCARBONS; Hydroxylases; KINETICS; Ligands; Macromolecular Substances; MEMBRANE PROTEINS; Molecular and cellular biology; Molecular Sequence Data; Molecular Weight; Neuropeptide receptors; Oligonucleotide Probes; ORGANIC CHLORINE COMPOUNDS; ORGANIC COMPOUNDS; ORGANIC HALOGEN COMPOUNDS; Polychlorinated Dibenzodioxins - metabolism; POLYCYCLIC AROMATIC HYDROCARBONS; PROTEINS; Proteins - genetics; Proteins - metabolism; RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT; REACTION KINETICS; RECEPTORS; Receptors, Aryl Hydrocarbon; Receptors, Drug - genetics; Receptors, Drug - metabolism; RNA, Messenger - genetics; Sequence Homology, Nucleic Acid; Transcription Factors; Transfection; Human; Proteins; Intracellular transport; Complementary DNA; Consensus sequence; Activation; Aromatic compound; Molecular cloning; Comparative study; Aminoacid sequence; Xenobiotic; Biological receptor
• DOI: 10.1126/science.1852076
• ISSN: 0036-8075

The aryl hydrocarbon (Ah) receptor binds various environmental pollutants, such as polycyclic aromatic hydrocarbons, heterocyclic amines, and polychlorinated aromatic compounds (dioxins, dibenzofurans, and biphenyls), and mediates the carcinogenic effects of these agents. The complementary DNA and part of the gene for an 87-kilodalton human protein that is necessary for Ah receptor function have been cloned. The protein is not the ligand-binding subunit of the receptor but is a factor that is required for the ligand-binding subunit to translocate from the cytosol to the nucleus after binding ligand. The requirement for this factor distinguishes the Ah receptor from the glucocorticoid receptor, to which the Ah receptor has been presumed to be similar. Two portions of the 87-kilodalton protein share sequence similarities with two Drosophila proteins, Per and Sim. Another segment of the protein shows conformity to the consensus sequence for the basic helix-loop-helix motif found in proteins that bind DNA as homodimers or heterodimers.