TOXICOLOGICAL SCIENCES 124(1), 1–22 (2011) doi:10.1093/toxsci/kfr218 Advance Access publication September 9, 2011 Exactly the Same but Different: Promiscuity and Diversity in the Molecular Mechanisms of Action of the Aryl Hydrocarbon (Dioxin) Receptor Michael S. Denison,*,1 Anatoly A. Soshilov,* Guochun He,* Danica E. DeGroot,* and Bin Zhao† Downloaded from *Department of Environmental Toxicology, University of California, Davis, California 95616; and †Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China 1To whom correspondence should be addressed at Department of Environmental Toxicology, University of California, Meyer Hall, One Shields Avenue, Davis, CA 95616-8588. Fax: (530) 752-3394. E-mail:
[email protected]. http://toxsci.oxfordjournals.org/ Received June 6, 2011; accepted August 12, 2011 toxic effects in a wide range of species and tissues (Beischlag The Ah receptor (AhR) is a ligand-dependent transcription et al., 2008; Furness and Whelan, 2009; Hankinson, 2005; factor that mediates a wide range of biological and toxicological Humblet et al., 2008; Marinkovic´ et al., 2010; Poland and effects that result from exposure to a structurally diverse variety Knutson, 1982; Safe, 1990; White and Birnbaum, 2009). The of synthetic and naturally occurring chemicals. Although the overall mechanism of action of the AhR has been extensively best-characterized high-affinity ligands for the AhR include at University of California, Davis - Library on May 4, 2012 studied and involves a classical nuclear receptor mechanism of a wide variety of ubiquitous hydrophobic environmental action (i.e., ligand-dependent nuclear localization, protein hetero- contaminants such as the halogenated aromatic hydrocarbons dimerization, binding of liganded receptor as a protein complex to (HAHs) and nonhalogenated polycyclic aromatic hydrocarbons its specific DNA recognition sequence and activation of gene (PAHs).