Identification of a novel mechanism of regulation of Ah (dioxin) receptor function.

Ah receptor (AhR) is a ligand-activated transcription factor that mediates pleiotropic effects of environmental pollutants such as 2,3, 7,8-tetrachlorodibenzo-p-dioxin on host animals. In addition to induction of drug-metabolizing enzymes, the liganded AhR complex was found to activate gene expression of a factor designated AhR repressor (AhRR), which inhibits AhR function by competing with AhR for dimerizing with Arnt and binding to the XRE sequence. Thus, AhR and AhRR form a regulatory circuit in the xenobiotic signal transduction pathway and provide a novel mechanism of regulation of AhR function that may determine tissue-specific sensitivity to environmental pollutants.