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

Colin Flaveny, Gary H. Perdew, Charles A. Miller

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)57-62
Number of pages6
JournalToxicology Letters
Volume189
Issue number1
DOIs
StatePublished - Aug 25 2009

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Aryl Hydrocarbon Receptors
Gene expression
Ligands
Gene Expression
Proteins
Molecules
Protein Stability
Poisons
Xenobiotics
Viruses
Liver
Real-Time Polymerase Chain Reaction
Assays
Transcription Factors
Western Blotting
Chemical activation
Polychlorinated Dibenzodioxins

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

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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.",
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The Aryl-hydrocarbon receptor does not require the p23 co-chaperone for ligand binding and target gene expression in vivo. / Flaveny, Colin; Perdew, Gary H.; Miller, Charles A.

In: Toxicology Letters, Vol. 189, No. 1, 25.08.2009, p. 57-62.

Research output: Contribution to journalArticle

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AB - 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.

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