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- W2106817237 abstract "Abstract Using a variety of biochemical and cell-based approaches, we show that estrogen receptor α (ERα) is acetylated by the p300 acetylase in a ligand- and steroid receptor coactivator-dependent manner. Using mutagenesis and mass spectrometry, we identified two conserved lysine residues in ERα (Lys266 and Lys268) that are the primary targets of p300-mediated acetylation. These residues are acetylated in cells, as determined by immunoprecipitation-Western blotting experiments using an antibody that specifically recognizes ERα acetylated at Lys266 and Lys268. The acetylation of ERα by p300 is reversed by native cellular deacetylases, including trichostatin A-sensitive enzymes (i.e. class I and II deacetylases) and nicotinamide adenine dinucleotide-dependent/nicotinamide-sensitive enzymes (i.e. class III deacetylases, such as sirtuin 1). Acetylation at Lys266 and Lys268, or substitution of the same residues with glutamine (i.e. K266/268Q), a residue that mimics acetylated lysine, enhances the DNA binding activity of ERα in EMSAs. Likewise, substitution of Lys266 and Lys268 with glutamine enhances the ligand-dependent activity of ERα in a cell-based reporter gene assay. Collectively, our results implicate acetylation as a modulator of the ligand-dependent gene regulatory activity of ERα. Such regulation is likely to play a role in estrogen-dependent signaling outcomes in a variety of estrogen target tissues in both normal and pathological states." @default.
- W2106817237 created "2016-06-24" @default.
- W2106817237 creator A5006798582 @default.
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- W2106817237 creator A5055336978 @default.
- W2106817237 creator A5075810655 @default.
- W2106817237 creator A5076677012 @default.
- W2106817237 date "2006-07-01" @default.
- W2106817237 modified "2023-10-01" @default.
- W2106817237 title "Acetylation of Estrogen Receptor α by p300 at Lysines 266 and 268 Enhances the Deoxyribonucleic Acid Binding and Transactivation Activities of the Receptor" @default.
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- W2106817237 doi "https://doi.org/10.1210/me.2005-0531" @default.
- W2106817237 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1483068" @default.
- W2106817237 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16497729" @default.
- W2106817237 hasPublicationYear "2006" @default.
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