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• W1985298972 endingPage "1633" @default.
• W1985298972 startingPage "1623" @default.
• W1985298972 abstract "To assess the importance of transactivation domains (TAD), DNA binding and transcription on the degradation of the AH receptor (AHR), Hepa-1 cells were pre-treated with actinomycin D (AD) or cycloheximide (CHX) and exposed to 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). AD or CHX did not affect nuclear localization or DNA binding of the AHR but inhibited ligand-induced degradation. In contrast, AD or CHX did not inhibit geldanamycin (GA) induced degradation of the AHR. To assess the role of the COOH-terminal TAD in AHR degradation, stop codons were placed at nucleotide 1501 and 1921 of the Ahb−1 AHR coding region to generate AHR500 and AHR640. Stable cell lines were generated and exposed to TCDD. Cells expressing AHR500 did not induce CYP1A1 protein, but exhibited significant degradation of AHR500. Cells expressing AHR640 induced CYP1A1 protein to 50% of the level of cells expressing wild type AHR and exhibited significant degradation of AHR640. Importantly, AD and CHX did not inhibit the TCDD-induced degradation of either AHR500 and AHR640 and these receptors showed a more rapid profile of ligand-induced degradation compared to cells expressing wild type AHR. TCDD exposure to Hepa-1 cells with reduced aryl hydrocarbon receptor nuclear translocator (ARNT), showed ligand-induced degradation of the AHR that was not blocked by AD. However, AD inhibited TCDD-induced degradation when ARNT expression was restored. These results show that multiple mechanisms exist for the ligand and GA-induced degradation of the AHR and suggest that ligand-induced degradation can switch between two mechanisms depending on the presence of a functional TAD and the binding to DNA." @default.
• W1985298972 created "2016-06-24" @default.
• W1985298972 creator A5010878144 @default.
• W1985298972 creator A5082287001 @default.
• W1985298972 creator A5083479844 @default.
• W1985298972 date "2005-11-01" @default.
• W1985298972 modified "2023-10-15" @default.
• W1985298972 title "Role of the carboxy-terminal transactivation domain and active transcription in the ligand-induced and ligand-independent degradation of the mouse Ahb−1 receptor" @default.
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• W1985298972 doi "https://doi.org/10.1016/j.bcp.2005.09.006" @default.
• W1985298972 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16226227" @default.
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