title: Repression of aryl hydrocarbon receptor transcriptional activity by epidermal growth factor.
abstract: The aryl hydrocarbon receptor (AHR) mediates most, if not all, of the many toxicological effects of the environmental pollutant 2,3,7,8-tetrachlorodibenzo- p-dioxin [(TCDD) or dioxin]. The "classical" pathway of AHR action involves dimerization of the liganded AHR with the aryl hydrocarbon nuclear translocator (ARNT) protein, and the AHR-ARNT dimer specifically associates with the enhancer regions of dioxin-responsive genes, leading to their increased transcription. Sutter and coworkers recently reported that epidermal growth factor (EGF) represses the dioxin-mediated induction of CYP1A1 in cultured normal human keratinocytes by inhibiting the recruitment of the transcriptional coactivator protein p300 to the CYP1A1 gene. EGF also inhibits the dioxin-dependent induction of certain parameters in keratinocytes that are reflective of dioxin-induced chloracne. These findings point to the potential usefulness of EGF for the treatment of chloracne and also describe a novel mechanism for repression of dioxin-induced gene transcription.
authors: Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, and Molecular Toxicology Program, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA. ohank@mednet.ucla.edu
authors: Oliver
authors: O
authors: Hankinson
mesh_terms: D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics / Q000378:metabolism; D054506:Chloracne / Q000235:genetics* / Q000378:metabolism; D004147:Dioxins / Q000378:metabolism / Q000633:toxicity; D015536:Down-Regulation; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004147:Dioxins; D018336:Receptors, Aryl Hydrocarbon; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D004815:Epidermal Growth Factor