The Aryl-hydrocarbon receptor does not require the p23 co-chaperone for ligand binding and target gene expression in vivo.

The Aryl-hydrocarbon receptor (Ahr) is a ligand-activated transcription factor that mediates most of the toxic affects of 2,3,7,8-tetrachlorodibenzo-(p)-dioxin (TCDD) and other xenobiotic compounds. The AHR cytoplasmic complex consists of two molecules of HSP90 and at least one molecule of Hepatitis B Virus-X associated protein 2 and the co-chaperone p23. With the use of in vitro model systems, p23 has been shown previously to be important to maintaining the efficient ligand binding and subsequent downstream inducibility of the AHR. In this study we attempted to identify the role p23 plays in AHR signaling in vivo using a p23 null mouse. Ligand binding assays and western blot analysis revealed that p23 was not required for AHR protein stability and competent ligand binding in liver. Real-time RT-PCR analysis conducted on p23 null, heterozygous and homozygous mice suggested that p23 is dispensable for stable AHR protein levels, or efficient TCDD-mediated AHR activation of Cyp1a1 and Cyp1a2.