Cited by 899Toxic Organic Pollutants ImpactPharmacogenetics and Drug MetabolismGenomics, phytochemicals, and oxidative stress

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AH RECEPTOR SIGNALING PATHWAYS

Schmidt, Jennifer V., Bradfield, Christopher A.·1996·Annual Review of Cell and Developmental Biology

DOI 10.1146/annurev.cellbio.12.1.55

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Abstract

▪ Abstract The aryl hydrocarbon (Ah) receptor has occupied the attention of toxicologists for over two decades. Interest arose from the early observation that this soluble protein played key roles in the adaptive metabolic response to polycyclic aromatic hydrocarbons and in the toxic mechanism of halogenated dioxins and dibenzofurans. More recent investigations have provided a fairly clear picture of the primary adaptive signaling pathway, from agonist binding to the transcriptional activation of genes involved in the metabolism of xenobiotics. Structure-activity studies have provided an understanding of the pharmacology of this receptor; recombinant DNA approaches have identified the enhancer sequences through which this factor regulates gene expression; and functional analysis of cloned cDNAs has allowed the characterization of the major signaling components in this pathway. Our objective is to review the Ah receptor's role in regulation of xenobiotic metabolism and use this model as a framework for understanding the less well-characterized mechanism of dioxin toxicity. In addition, it is hoped that this information can serve as a model for future efforts to understand an emerging superfamily of related signaling pathways that control biological responses to an array of environmental stimuli.

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Authors: Schmidt, J. V., & Bradfield, C. A.
Affiliations: Northwestern University (US)
University of Wisconsin–Madison (US)
ORCID: Schmidt, Jennifer V.
Bradfield, Christopher A.
Venue: Annual Review of Cell and Developmental Biology
Publisher: Annual Reviews
Published: 1996-11
Volume: 12
Issue: 1
Pages: 55-89
ISSN: 1081-0706 (ISSN-L)
1530-8995
DOI: 10.1146/annurev.cellbio.12.1.55
OpenAlex: W2133972226
Cited by: 899
References: 140
Citations by year: 2026: 3 · 2025: 9 · 2024: 3 · 2023: 16 · 2022: 10 · 2021: 20 · 2020: 16 · 2019: 17 · 2018: 28 · 2017: 29 · 2016: 16 · 2015: 19 · 2014: 28 · 2013: 27 · 2012: 26
FWCI: 11.14
Type: journal article
Language: en
Open access: closed
Locations: Annual Review of Cell and Developmental Biology (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute (CA09560, T32CA009560)
National Institute of Environmental Health Sciences (ES06883, R01ES006883)
Topics: Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Keywords: aryl hydrocarbon receptor, dioxin toxicity, dibenzofuran, polycyclic aromatic hydrocarbons, xenobiotic metabolism, transcriptional activation, gene expression regulation, enhancers, structure-activity relationship, signaling pathways, ecotoxicology
MeSH terms: Amino Acid Sequence, Animals, Binding Sites, Dioxins, Humans, Molecular Sequence Data, Peptide Mapping, Signal Transduction, Receptors, Aryl Hydrocarbon, Mice, Knockout, Mice

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