title: The Aryl-hydrocarbon receptor does not require the p23 co-chaperone for ligand binding and target gene expression in vivo.
abstract: 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.
authors.affiliation: Department of Veterinary and Biomedical Sciences and Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Colin
authors.initials: C
authors.lastname: Flaveny
authors.forename: Gary H
authors.initials: GH
authors.lastname: Perdew
authors.forename: Charles A
authors.initials: CA
authors.lastname: Miller
mesh_terms: D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006579:Heterozygote; D006720:Homozygote; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000502:physiology*; D008024:Ligands; D008099:Liver / Q000187:drug effects / Q000196:embryology / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism / Q000633:toxicity*; D000071876:Prostaglandin-E Synthases; D011485:Protein Binding; D055550:Protein Stability; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*
chemical_list: D008024:Ligands; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605868:Ptges3 protein, mouse