The role of the aryl hydrocarbon receptor nuclear translocator protein in aryl hydrocarbon receptor action

Abstract

The aryl hydrocarbon (AH, or dioxin) receptor mediates carcinogenesis by a wide variety of compounds. It acts as a ligand-dependent transcription factor. Many investigators expected that the AH receptor would prove to be a member of the steroid/thyroid/retinoic acid receptor superfamily of proteins. However, recent cloning of the two subunits of the DNA-binding form of the AH receptor has shown that this is not the case. These subunits, the AH receptor nuclear translocator protein (ARNT) and the ligand-binding AH receptor monomer, do not contain zinc finger DNA-binding domains, nor do they have any other sequence similarities with members of the above family. Instead, they both contain basic helix-loop-helix (bHLH) motifs and also another segment of sequence similarity, the “PAS” region. bHLH motifs in other transcription factors are known to function as dimerization and DNA-binding domains. Present experiments are directed toward understanding the mechanisms of action and the roles of the two subunits.