The genetics of aryl hydrocarbon hydroxylase induction in mice: A single gene difference between C57BL/6J and DBA/2J

Thomas, Paul E.; Kouri, Richard E.; Hutton, John J.

doi:10.1007/bf00486400

Cited by 183 publications

(56 citation statements)

References 17 publications

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“…C57BL/6J mice exhibit enhanced induction of many antixenobiotic activities relative to DBA/2J mice due to differences in the arylhydrocarbon receptor (23,25,63). However, the Ahr gene, which encodes this receptor, is on chromosome 12 in the mouse genome and not included in the QTL regions mapped here.…”

Section: Discussionmentioning

confidence: 87%

Genetic loci that affect aristolochic acid-induced nephrotoxicity in the mouse

Rosenquist

2011

American Journal of Physiology-Renal Physiology

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Section: Discussionmentioning

confidence: 87%

Genetic loci that affect aristolochic acid-induced nephrotoxicity in the mouse

Rosenquist

2011

American Journal of Physiology-Renal Physiology

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“…The AHR has been shown to be activated by diverse environmental toxicants and endogenous ligands, and play an important role in adaptive metabolism, dioxin toxicity, and normal vascular and immune development (1, 2), ever since it was identified four decades ago for mediating metabolic responses to aryl hydrocarbon toxicants (3,4) and the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (5). The AHR was more recently found to mediate diverse cellular and physiological responses and likely respond to unknown endogenous AHR ligands (1,2,(6)(7)(8).…”

mentioning

confidence: 99%

Structural hierarchy controlling dimerization and target DNA recognition in the AHR transcriptional complex

Seok

Lee²,

Li³

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

106

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The aryl hydrocarbon receptor (AHR) belongs to the PAS (PER-ARNT-SIM) family transcription factors and mediates broad responses to numerous environmental pollutants and cellular metabolites, modulating diverse biological processes from adaptive metabolism, acute toxicity, to normal physiology of vascular and immune systems. The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. We determined the crystal structure of the mammalian AHR-ARNT heterodimer in complex with the DRE, in which ARNT curls around AHR into a highly intertwined asymmetric architecture, with extensive heterodimerization interfaces and AHR interdomain interactions. Specific recognition of the DRE is determined locally by the DNA-binding residues, which discriminates it from the closely related hypoxia response element (HRE), and is globally affected by the dimerization interfaces and interdomain interactions. Changes at the interdomain interactions caused either AHR constitutive nuclear localization or failure to translocate to nucleus, underlying an allosteric structural pathway for mediating ligand-induced exposure of nuclear localization signal. These observations, together with the global higher flexibility of the AHR PAS-A and its loosely packed structural elements, suggest a dynamic structural hierarchy for complex scenarios of AHR activation induced by its diverse ligands.he aryl hydrocarbon receptor (AHR) belongs to the PER-ARNT-SIM (PAS) family transcription factor that mediates broad responses to cellular and environmental cues. The AHR has been shown to be activated by diverse environmental toxicants and endogenous ligands, and play an important role in adaptive metabolism, dioxin toxicity, and normal vascular and immune development (1, 2), ever since it was identified four decades ago for mediating metabolic responses to aryl hydrocarbon toxicants (3, 4) and the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (5). The AHR was more recently found to mediate diverse cellular and physiological responses and likely respond to unknown endogenous AHR ligands (1, 2, 6-8). Developmentally, the AHR plays a role in the normal development and function of both the vascular and immune systems (9-12), and has close links to cancer, metabolic, immune, and cardiovascular diseases (13-18).Intense efforts in the past four decades have yielded important insights into the molecular processes governing AHR signaling. Newly synthesized AHR is located in cytosol and associated with the chaperones Hsp90 (19), P23 (20, 21), and AHR associated protein 9 (ARA9, also known as XAP2 or AIP) (22-24). Binding of ligands induces conformational changes in the AHR that lead to exposure of nuclear localization sequences (NLS) (25, 26). Following nuclear translocation, the AHR exchanges chaperones for a transcription partner, ARNT (1) and the AHR-ARNT heterodimer binds near the promoters of target genes at dioxin-response element (DRE...

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“…Crossing the two strains yielded a strain with intermediate responsiveness and backcrossing revealed that the ability to respond was dependent on one locus, named the Aryl Hydrocarbon responsiveness (Ah) locus (Thomas et al, 1972). Poland et al characterized the putative gene product, a cytosolic protein that could bind to radiolabeled TCDD .…”

Section: Ahr Is Required For Toxic Effects Ofhahmentioning

confidence: 99%

Characterization of an aryl hydrocarbon receptor from a cetacean : an approach for assessing contaminant susceptibility in protected species

Jensen¹

2000

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The genetics of aryl hydrocarbon hydroxylase induction in mice: A single gene difference between C57BL/6J and DBA/2J

Cited by 183 publications

References 17 publications

Genetic loci that affect aristolochic acid-induced nephrotoxicity in the mouse

Genetic loci that affect aristolochic acid-induced nephrotoxicity in the mouse

Structural hierarchy controlling dimerization and target DNA recognition in the AHR transcriptional complex

Characterization of an aryl hydrocarbon receptor from a cetacean : an approach for assessing contaminant susceptibility in protected species

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