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- W2728268528 abstract "The aryl hydrocarbon receptor (AHR) mediates the toxic effects of halogenated aromatic hydrocarbons (HAHs), including 2,3,7,8-tetrachlorodibenzo-p-dioxin, 2,3,4,7,8-pentachlorodibenzofuran and 2,3,7,8-tetrachlorodibenzofuran. Y322 is believed to play a role in binding-independent activation of AHR by atypical inducers, such as omeprazole. I examined AHR-mediated regulation of and coactivator recruitment to CYP1A1, CYP1B1, HES1 and TiPARP in T-47D and HuH7 cells. All compounds induced expression of each gene in both cell lines, with some temporal differences between the HAHs and omeprazole. Chromatin immunoprecipitation assays demonstrated activator-, cell line- and gene-selectivity in AHR coactivator recruitment. Omeprazole induced AHR degradation which was prevented by MG-132 pre-treatment. Y322 was found to be important for maximal AHR activation by 2,3,7,8-TCDD and 2,3,4,7,8-PeCDF, but required for 2,3,7,8-TCDF and Omp in an AHR-deficient MCF-7 cells. My findings provide further evidence for cell-, gene- and ligand-dependent differences in AHR-mediated gene expression and coactivator recruitment, and a role for Y322 in AHR activation.%%%%MAST" @default.
- W2728268528 created "2017-07-14" @default.
- W2728268528 creator A5055530215 @default.
- W2728268528 date "2011-08-25" @default.
- W2728268528 modified "2023-09-27" @default.
- W2728268528 title "Modulation of Aryl Hydrocarbon Receptor-dependent Transcription by Halogenated Compounds and Pharmaceuticals" @default.
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