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• W2009878296 abstract "Transcriptional responses to estrogens are controlled by the cell- and gene-specific interactions of the nuclear estrogen receptor (ER) with cofactors and other transcription factors. The pituitary-specific PRL enhancer/promoter is regulated by estrogens only when it is bound by both ER and the pituitary-specific transcription factor, Pit-1. Cooperative ER/Pit-1 activation of the dormant PRL enhancer/promoter in pituitary progenitor cells requires the estrogen-dependent activation function-2 (AF-2) of ER, but is inhibited by one AF-2-interacting cofactor, RIP140. Here, the complex actions of RIP140 and other AF-2-interacting proteins at the PRL enhancer/promoter were shown to operate via ER itself. RIP140 inhibition of ER/Pit-1 activation in the absence of AF-1 and RIP140 inhibition of both ER alpha and ER beta cooperative activation with Pit-1 suggested a conserved ER site for RIP140 action, possibly AF-2. Coexpression of other AF-2-interacting proteins, including the p160 factors, steroid receptor coactivator-1a (SRC-1a) and glucocorticoid receptor interacting protein-1 (GRIP1), had negligible effects on ER alpha/Pit-1 cooperative activation, but partially relieved RIP140 inhibition. Relief of RIP140 inhibition required the AF-2-binding, LXXLL motifs in SRC-1a and GRIP1. An ER AF-2 mutant that selectively blocked ER interaction with p160s, but not RIP140, still cooperated with Pit-1 and was inhibited by RIP140, but was not relieved by SRC-1a or GRIP1 expression. Thus, SRC-1a and GRIP1 binding to AF-2 counteracted the inhibition of ER/Pit-1 activation by another AF-2-interacting protein, RIP140. Complex, sometimes antagonistic, actions of different classes of AF-2-interacting proteins may play an important role in the cell- and gene-specific estrogen regulation of PRL and other genes." @default.
• W2009878296 created "2016-06-24" @default.
• W2009878296 creator A5045803872 @default.
• W2009878296 date "1999-06-01" @default.
• W2009878296 modified "2023-10-13" @default.
• W2009878296 title "Regulation of Estrogen Receptor Activation of the Prolactin Enhancer/Promoter by Antagonistic Activation Function-2-Interacting Proteins" @default.
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• W2009878296 doi "https://doi.org/10.1210/mend.13.6.0298" @default.
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