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Cited by 831Toxic Organic Pollutants ImpactPharmacogenetics and Drug MetabolismPeroxisome Proliferator-Activated Receptors

Cloning of the Ah-receptor cDNA reveals a distinctive ligand-activated transcription factor.

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Burbach, K M, Poland, A, Bradfield, C A·1992·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.89.17.8185PMC PMC49882
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Abstract

A cDNA encoding the murine Ah receptor (Ahb-1 allele for aromatic hydrocarbon responsiveness) has been isolated and characterized. Analysis of the deduced protein sequence revealed a region with similarity to the basic region/helix-loop-helix (BR/HLH) motif found in many transcription factors that undergo dimerization for function. In addition to the BR/HLH domain, the N-terminal domain of the Ah receptor has extensive sequence similarity to the human ARNT (aryl hydrocarbon receptor nuclear translocator) protein and two regulatory proteins of Drosophila, Sim and Per. Photoaffinity labeling and peptide mapping studies indicate that the Ah receptor binds agonist at a domain that lies within this conserved N-terminal domain. The Ah receptor appears to be a ligand-activated transcription factor with a helix-loop-helix motif similar to those found in a variety of DNA-binding proteins, including Myc and MyoD.

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  • The bHLH domain of AHR is responsible for nuclear localization, DNA binding, and dimerization with ARNT.

    “The bHLH domain has been shown to be responsible for nuclear localization, DNA binding, and dimerization with the obligate partner, the Aryl Hydrocarbon Nuclear Translocator (ARNT) (Burbach et al., 1992; Bert N. Fukunaga & Hankinson, 1996; Sanjay Jain et al., 1994).”

    From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as Burbach et al., 1992

    The Abstract (page not specified in our copy) identifies an AHR bHLH-like motif and links that motif to transcription factors that dimerize and bind DNA. It reports sequence similarity to ARNT, but does not establish that the bHLH domain is responsible for nuclear localization, DNA binding, or dimerization specifically with ARNT. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Mapping experiments revealed that residue 375 mapped to the ligand binding domain, supporting the identity of this residue as essential for ligand affinity.

    “Mapping experiments revealed that residue 375 mapped to the ligand binding domain, supporting the identity of this residue as essential for ligand affinity (Burbach et al., 1992; Ema et al., 1994; Xing et al., 2012).”

    From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as Burbach et al., 1992

    The Abstract (p. 8185) says photoaffinity labeling and peptide mapping placed an Ah-receptor agonist-binding domain within the conserved N-terminal domain. Our copy does not identify residue 375 or establish that it is essential for ligand affinity. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Burbach, K. M., Poland, A., & Bradfield, C. A.
Affiliations
Northwestern University (US)
ORCID
Bradfield, C A
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1992-09
Volume
89
Issue
17
Pages
8185-8189
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.89.17.8185
PMC
PMC49882
OpenAlex
W2087332917
Cited by
831
References
1
Citations by year
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FWCI
50.42
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Cancer Society
  • Otho S. A. Sprague Memorial Institute
  • National Cancer Institute (T32 CA09560, T32 CA09560-06, T32CA009560)
  • National Institute of Environmental Health Sciences (ES-01884, ES-05703)
  • Air Force Office of Scientific Research
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 › Peroxisome Proliferator-Activated Receptors
Keywords
aryl hydrocarbon receptor, cDNA cloning, ligand-activated transcription factors, ARNT, N-terminal domain, agonist binding site, photoaffinity labeling, peptide mapping, c-Myc, MyoD
MeSH terms
Amino Acid Sequence, Animals, Cloning, Molecular, DNA, Molecular Sequence Data, Peptide Fragments, Peptide Mapping, Receptors, Drug, RNA, Messenger, Transcription Factors, Tumor Cells, Cultured, Restriction Mapping, Gene Expression, Consensus Sequence, Sequence Alignment, Receptors, Aryl Hydrocarbon, Mice, In Vitro Techniques

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