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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Relative Contributions of Affinity and Intrinsic Efficacy to Aryl Hydrocarbon Receptor Ligand Potency
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Kynurenine importation by SLC7A11 propagates anti-ferroptotic signaling
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Ah receptor and NF-κB interactions: mechanisms and physiological implications
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2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters the mRNA expression of critical genes associated with cholesterol metabolism, bile acid biosynthesis, and bile transport in rat liver: A microarray study
Fletcher, N., Wahlström, D., Lundberg, R., Nilsson, C. B., Nilsson, K. C., Stockling, K., Hellmold, H., & Håkansson, H. (2005) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2004.12.003 · Cited by 174
The Role of Aryl Hydrocarbon Receptor in the Pathogenesis of Cardiovascular Diseases
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The role of the aryl hydrocarbon receptor in the female reproductive system
Hernández‐Ochoa, I., Karman, B. N., & Flaws, J. A. (2008) · Biochemical Pharmacology · doi:10.1016/j.bcp.2008.09.037 · Cited by 171
Zebrafish as a novel experimental model for developmental toxicology
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Epigallocatechin Gallate Inhibits Aryl Hydrocarbon Receptor Gene Transcription through an Indirect Mechanism Involving Binding to a 90 kDa Heat Shock Protein
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Reproductive and developmental toxicity of dioxin in fish
King‐Heiden, T. C., Mehta, V., Xiong, K. M., Lanham, K. A., Antkiewicz, D. S., Ganser, A. M., Heideman, W., & Peterson, R. E. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.09.027 · Cited by 167
Applications of Gene Arrays in Environmental Toxicology: Fingerprints of Gene Regulation Associated with Cadmium Chloride, Benzo(a)pyrene, and Trichloroethylene
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Aryl Hydrocarbon Receptor Activation by TCDD Reduces Inflammation Associated with Crohn's Disease
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Structural and Functional Characterization of the Aryl Hydrocarbon Receptor Ligand Binding Domain by Homology Modeling and Mutational Analysis
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Repression of Aryl Hydrocarbon Receptor (AHR) Signaling by AHR Repressor: Role of DNA Binding and Competition for AHR Nuclear Translocator
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Aryl Hydrocarbon Receptor-Deficient Mice Generate Normal Immune Responses to Model Antigens and Are Resistant to TCDD-Induced Immune Suppression
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Identification and Functional Characterization of Two Highly Divergent Aryl Hydrocarbon Receptors (AHR1 and AHR2) in the TeleostFundulus heteroclitus
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Aryl Hydrocarbon Receptor Activation Produces Heart-Specific Transcriptional and Toxic Responses in Developing Zebrafish
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The Aryl Hydrocarbon Receptor Displaces p300 from E2F-dependent Promoters and Represses S Phase-specific Gene Expression
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Trace derivatives of kynurenine potently activate the aryl hydrocarbon receptor (AHR)
Seok, S.-H., Ma, Z.-X., Feltenberger, J. B., Chen, H., Chen, H., Scarlett, C., Lin, Z., Satyshur, K. A., Cortopassi, M., Jefcoate, C. R., et al. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra117.000631 · Cited by 157
“with diverse shape and chemical properties have been reported to bind AHR (28, 29).”
BackgroundSelf-citation
The Aryl Hydrocarbon Receptor Mediates UVB Radiation–Induced Skin Tanning
Jux, B., Kadow, S., Luecke, S., Rannug, A., Krutmann, J., & Esser, C. (2011) · Journal of Investigative Dermatology · doi:10.1038/jid.2010.269 · Cited by 156
DNA binding and protein interactions of the AHR/ARNT heterodimer that facilitate gene activation.
Swanson, H. I. (2002) · Chemico-Biological Interactions · doi:10.1016/s0009-2797(02)00066-2 · Cited by 158
Unexpected diversity of aryl hydrocarbon receptors in non‐mammalian vertebrates: insights from comparative genomics
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A role for the aryl hydrocarbon receptor and the dioxin TCDD in rheumatoid arthritis
Kobayashi, S., Okamoto, H., Iwamoto, T., Toyama, Y., Tomatsu, T., Yamanaka, H., & Momohara, S. (2008) · Lara D. Veeken · doi:10.1093/rheumatology/ken259 · Cited by 155
Translesion Synthesis by Human DNA Polymerase κ on a DNA Template Containing a Single Stereoisomer of dG-(+)- or dG-(−)-anti-N2-BPDE (7,8-Dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene)
Suzuki, N., Ohashi, E., Kolbanovskiy, A., Geacintov, N. E., Grollman, A. P., Ohmori, H., & Shibutani, S. (2002) · Biochemistry · doi:10.1021/bi020049c · Cited by 155
AHR1B, a new functional aryl hydrocarbon receptor in zebrafish: tandem arrangement of ahr1b and ahr2 genes
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Induction of Mouse UDP-Glucuronosyltransferase mRNA Expression in Liver and Intestine by Activators of Aryl-Hydrocarbon Receptor, Constitutive Androstane Receptor, Pregnane X Receptor, Peroxisome Proliferator-Activated Receptor α, and Nuclear Factor Erythroid 2-Related Factor 2
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PD98059 Is an Equipotent Antagonist of the Aryl Hydrocarbon Receptor and Inhibitor of Mitogen-Activated Protein Kinase Kinase
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Aryl Hydrocarbon Receptor Is Critical for Homeostasis of Invariant γδ T Cells in the Murine Epidermis
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Deciphering the Nutraceutical Potential of Raphanus sativus—A Comprehensive Overview
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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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