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• W2015132346 endingPage "985" @default.
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• W2015132346 abstract "The role of GR phosphorylation in modulating GR-mediated transcription is not fully understood. Here we show that the hGR is rapidly phosphorylated at S211 and S226 in response to the synthetic agonist dexamethasone (dex) in COS-1 cells. Using a triple phosphorylation mutant hGR construct, we demonstrate that phosphorylation at one or more S residues (from S203, S211, and S226) is required for maximal hGR-mediated transcriptional activation on the MMTV promoter in response to dex in COS-1 cells, but that this effect is promoter selective. Phosphorylation at these residues does not affect unliganded or agonist-induced hGR degradation, suggesting that the mechanism whereby hGR phosphorylation at these residues regulates GR-mediated transactivation via a GRE does not involve changes in GR half-life. We have previously shown a direct correlation between efficacy for transactivation and interaction of the hGR with glucocorticoid receptor interacting protein-1 (GRIP-1). Here we show by pull-down assays in the absence and presence of glucocorticoid response elements (GREs) that phosphorylation of the hGR is required for GR-GRIP-1 interaction. Chromatin immunoprecipitation (ChIP) assays revealed that hGR phosphorylation at one or more S residues (from S226, S211, and S203) is required for the recruitment of GRIP-1 to the synthetic MMTV promoter as well as to the endogenous GRE-containing glucocorticoid-induced leucine zipper (GILZ) promoter in intact COS-1 cells, but not for nuclear localization. Our results support the conclusion that phosphorylation at S203, S211, and/or S226 of the hGR is required for a maximal transcriptional response via the synthetic MMTV and endogenous GILZ GREs in COS-1 cells, to enable recruitment of GRIP-1 to the hGR." @default.
• W2015132346 created "2016-06-24" @default.
• W2015132346 creator A5014676071 @default.
• W2015132346 creator A5058466834 @default.
• W2015132346 creator A5067887867 @default.
• W2015132346 date "2010-01-12" @default.
• W2015132346 modified "2023-10-01" @default.
• W2015132346 title "Glucocorticoid Receptor Phosphorylation Modulates Transcription Efficacy through GRIP-1 Recruitment" @default.
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• W2015132346 doi "https://doi.org/10.1021/bi901956s" @default.
• W2015132346 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20047289" @default.
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