The ah-receptor: Genetics, structure and function

The AH-receptor is a ligand-activated transcription factor that regulates a number of biological responses to planar aromatic hydrocarbons. Interest in this receptor is related to its role in the toxic action of a variety of environmental chemicals, the simplicity and elegance of the murine genetics that led to its characterization and the distinctive mechanism by which this receptor activates gene expression. Recent cloning experiments have demonstrated that the AH-receptor is structurally related to the Per, ARNT and Sim proteins. Members of this newly described gene family are characterized by two N-terminal domains, the most characteristic of which is a motif referred to as a PAS domain. In the AH-receptor, this domain harbours sequences involved in the formation of a hydrophobic pocket that bind receptor agonists. Adjacent to the PAS domain in the AH-receptor, ARNT and Sim proteins is a basic/helix-loop-helix (bHLH) domain that appears to mediate heterodimerization and sequence specific DNA binding properties. The observation that the bHLH domain is present in the AH-receptor and the ARNT protein, a factor required for proper AH-receptor function, suggests that these proteins are heterodimeric partners that activate gene expression in a manner similar to Myc/Max and MyoD/E2A. The objectives of this review are to describe recent experimental results in this field and to use this information to develop a molecular model of AH-receptor mediated signal transduction.