The aryl hydrocarbon receptor: a comparative perspective

Abstract

The aryl hydrocarbon receptor (Ah receptor or AHR) is a ligand-activated transcription factor involved in the regulation of several genes, including those for xenobiotic-metabolizing enzymes such as cytochrome P450 1A and 1B forms. Ligands for the AHR include a variety of aromatic hydrocarbons, including the chlorinated dioxins and related halogenated aromatic hydrocarbons whose toxicity occurs through activation of the AHR. The AHR and its dimerization partner ARNT are members of the emerging bHLH-PAS family of transcriptional regulatory proteins. In this review, our current understanding of the AHR signal transduction pathway in non-mammalian and other non-traditional species is summarized, with an emphasis on similarities and differences in comparison to the AHR pathway in rodents and humans. Evidence and prospects for the presence of a functional AHR in early vertebrates and invertebrates are also examined. An overview of the bHLH-PAS family is presented in relation to the diversity of bHLH-PAS proteins and the functional and evolutionary relationships of the AHR and ARNT to the other members of this family. Finally, some of the most promising directions for future research on the comparative biochemistry and molecular biology of the AHR and ARNT are discussed.