title: Exactly the same but different: promiscuity and diversity in the molecular mechanisms of action of the aryl hydrocarbon (dioxin) receptor.
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.
authors: Department of Environmental Toxicology, University of California, Davis, California 95616, USA. msdenison@ucdavis.edu
authors: Michael S
authors: MS
authors: Denison
authors: Anatoly A
authors: AA
authors: Soshilov
authors: Guochun
authors: G
authors: He
authors: Danica E
authors: DE
authors: DeGroot
authors: Bin
authors: B
authors: Zhao
mesh_terms: D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D015870:Gene Expression; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D000072317:Polychlorinated Dibenzodioxins / Q000493:pharmacokinetics / Q000633:toxicity; D011485:Protein Binding; D018336:Receptors, Aryl Hydrocarbon / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction; D013045:Species Specificity
chemical_list: D008024:Ligands; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D018160:Receptors, Cytoplasmic and Nuclear