Seminars in Cell & Developmental Biology : Mediator-dependent nuclear receptor functions. Volume 22, Issue 7, September 2011, Pages 749–758 Edited By Dr Tomas Obsil and Dr Kathryn Hentges Abstract As gene-specific transcription factors, nuclear receptors are broadly involved in many important biological processes. Their function on target genes requires the stepwise assembly of different coactivator complexes that facilitate chromatin remodeling and subsequent preinitiation complex (PIC) formation and function. Highlights ► We discussed gene-specific mediator functions and mechanisms. ► The conventional nuclear receptor–Mediator pathway is conditionally required. ► New alternative Mediator–NR pathways are elucidated. ► Physiological processes linked to nuclear receptor–Mediator interactions are summarized. ► How Mediator transmits signals from nuclear receptors to the general transcription machinery. Keywords Nuclear receptor; Mediator; Coactivator; Corepressor; Transcription; Chromatin; Ligands; LXXLL motif; AF-2 domain Copyright © 2011 Elsevier Ltd.
Ligand entry pathways in the ligand binding domain... [FEBS Lett. 2011] - PubMed result. Discovery of GSK1997132B a novel centrally penetra... [Bioorg Med Chem Lett. 2011] - PubMed result. Protein evolution by molecular tinkering: diversif... [PLoS Biol. 2010] - PubMed result. Nr_alignment_tree.jpg (JPEG Image, 2999x2249 pixels) - Scaled (27. Intrinsic disorder of Drosophila melanogaster horm... [Proteins. 2011] - PubMed result. A conserved surface on the ligand bindin... [Mol Cell Endocrinol. 2011. Cancer Cell : Regression of Castrate-Recurrent Prostate Cancer by a Small-Molecule Inhibitor of the Amino-Terminus Domain of the Androgen Receptor. To view the full text, please login as a subscribed user or purchase a subscription. Click here to view the full text on ScienceDirect. Figure 1 EPI-001 Blocks AR Transcriptional Activity (A) Chemical structures of EPI-001 (BADGE.H2O.HCl) or the inactive analog 185-9-1 (BADGE.2H2O).
(B) Transactivation assays of the AR NTD were performed in LNCaP cells cotransfected with p5 × Gal4UAS-TATA-luciferase and either AR-(1-558)-Gal4 DBD, Gal4DBD-CREB prior to incubation with FSK or IL-6 or vehicle for 24 hr. (C) IC50s of EPI-001 versus 185-9-1 on AR NTD transactivation were examined in LNCaP cells with varying concentrations of EPI-001 and 185-9-1. (D) EPI-001 inhibits both ligand-dependent and ligand-independent activation of the AR.
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