Repression of aryl hydrocarbon receptor transcriptional activity by epidermal growth factor.
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.
Hankinson
Oliver
O
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
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
D004147:Dioxins; D018336:Receptors, Aryl Hydrocarbon; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D004815:Epidermal Growth Factor