The aryl hydrocarbon receptor complex

Abstract

The heteromeric unliganded aryl hydrocarbon receptor complex (AHRC) contains the aryl hydrocarbon receptor monomer (AHR). Binding of polycyclic or halogenated aromatic hydrocarbon (PAH and HAH) ligand causes release of AHR, which then associates with the AHR nuclear translocator protein (ARNT) to generate the heterodimeric "transformed" AHRC. AHR and ARNT belong to a novel subclass of basic helix-loop-helix-containing transcription factors. The transformed AHRC binds xenobiotic responsive elements in responsive genes and turns on their transcription. Certain of these genes encode enzymes involved in the metabolic activation of PAHs to mutagenic derivatives. HAHs are not genotoxic: Their pathogenicity depends on the AHRC but not on their metabolism. Current research includes investigations directed towards delineating the pathways of HAH pathogenesis, ascertaining whether AHR can mediate signal transduction independently of DNA binding, understanding the mechanism of transcriptional activation, and investigating the potential roles of AHR and ARNT in development.