Peroxisome Proliferator-Activated Receptors and Retinoic Acid Receptors Differentially Control the Interactions of Retinoid X Receptor Heterodimers with Ligands, Coactivators, and Corepressors

• DOI: 10.1128/mcb.17.4.2166
• Publication Date: 2015-10-09T18:07:21Z
• Authors: James DiRenzo; Mats Söderström; Riki Kurokawa; Marie-Hélène Ogli...; Mercedes Ricote; Stephanie Ingrey; Andreas Hörlein; Michael G. Rosenfeld; Christopher K. Glass
• Keywords: Retinoid X receptor; Corepressor

AbstractAs the obligate member of most nuclear receptor heterodimers, retinoid X receptors (RXRs) can potentially perform two functions: cooperative binding to hormone response elements and coordinate regulation target genes by RXR ligands. In this paper we describe allosteric interactions between heterodimeric partners, retinoic acid (RARs) peroxisome proliferator-activated (PPARs); RARs PPARs prevent permit activation RXR-specific ligands, respectively. By competing for dimerization with on consisting direct-repeat half-sites spaced 1 bp (DR1 elements), relative abundance RAR PPAR determines whether signaling pathway will be functional. contrast RAR, which prevents ligands recruits corepressor N-CoR, permits SRC-1 in both Overexpression markedly potentiates ligand-dependent transcription PPARγ, suggesting that serves as a coactivator vivo. Remarkably, ability block interact corepressors requires CoR box, structural motif residing N-terminal region ligand domain. Mutations box convert from nonpermissive permissive partner DR1 elements. We suggest differential recruitment coactivators RAR-RXR PPAR-RXR heterodimers provides basis transcriptional switch may important controlling complex programs gene expression, such adipocyte differentiation.