Exactly the same but different

Promiscuity and diversity in the molecular mechanisms of action of the aryl hydrocarbon (dioxin) receptor

Michael S. Denison, Anatoly A. Soshilov, Guochun He, Danica E. Degroot, Bin Zhao

Research output: Contribution to journalArticle

362 Citations (Scopus)

Abstract

The Ah receptor (AhR) is a ligand-dependent transcription factor that mediates a wide range of biological and toxicological effects that result from exposure to a structurally diverse variety of synthetic and naturally occurring chemicals. Although the overall mechanism of action of the AhR has been extensively studied and involves a classical nuclear receptor mechanism of action (i.e., ligand-dependent nuclear localization, protein heterodimerization, binding of liganded receptor as a protein complex to its specific DNA recognition sequence and activation of gene expression), details of the exact molecular events that result in most AhR-dependent biochemical, physiological, and toxicological effects are generally lacking. Ongoing research efforts continue to describe an ever-expanding list of ligand-, species-, and tissue-specific spectrum of AhR-dependent biological and toxicological effects that seemingly add even more complexity to the mechanism. However, at the same time, these studies are also identifying and characterizing new pathways and molecular mechanisms by which the AhR exerts its actions and plays key modulatory roles in both endogenous developmental and physiological pathways and response to exogenous chemicals. Here we provide an overview of the classical and nonclassical mechanisms that can contribute to the differential sensitivity and diversity in responses observed in humans and other species following ligand-dependent activation of the AhR signal transduction pathway.

Original languageEnglish (US)
Article numberkfr218
Pages (from-to)1-22
Number of pages22
JournalToxicological Sciences
Volume124
Issue number1
DOIs
StatePublished - Nov 2011

Fingerprint

Aryl Hydrocarbon Receptors
Hydrocarbons
Toxicology
Ligands
Chemical activation
Signal transduction
Time and motion study
Time and Motion Studies
Cytoplasmic and Nuclear Receptors
Nuclear Proteins
Protein Binding
Gene expression
Signal Transduction
Transcription Factors
Tissue
Gene Expression
DNA
Research
Proteins

Keywords

  • Ah receptor
  • AhR
  • Dioxin
  • HAHs
  • Mechanism
  • PAHs
  • Promiscuity

ASJC Scopus subject areas

  • Toxicology

Cite this

Exactly the same but different : Promiscuity and diversity in the molecular mechanisms of action of the aryl hydrocarbon (dioxin) receptor. / Denison, Michael S.; Soshilov, Anatoly A.; He, Guochun; Degroot, Danica E.; Zhao, Bin.

In: Toxicological Sciences, Vol. 124, No. 1, kfr218, 11.2011, p. 1-22.

Research output: Contribution to journalArticle

Denison, Michael S. ; Soshilov, Anatoly A. ; He, Guochun ; Degroot, Danica E. ; Zhao, Bin. / Exactly the same but different : Promiscuity and diversity in the molecular mechanisms of action of the aryl hydrocarbon (dioxin) receptor. In: Toxicological Sciences. 2011 ; Vol. 124, No. 1. pp. 1-22.
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