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Inhibition Of Mammary Carcinoma Cell Growth By Rxr Is Mediated By The Receptor’s Oligomeric Switch.
J Mol Biol. 2010 Feb 23;
Authors: Yasmin R, Kannan-Thulasiraman P, Kagechika H, Dawson MI, Noy N
Ligands that activate the nuclear receptor RXR display potent anticarcinogenic activities but the mechanisms by which these compounds inhibit carcinoma cell growth are poorly understood. While RXR can regulate gene expression due to its intrinsic ligand-activated transcription function, this receptor can also regulate transcription by functioning as a ligand-controlled DNA architectural factor. It was thus reported that apo-RXR self-associates into tetramers and that each dimer within these tetramers can separately bind to an RXR response elements. Hence, DNA-binding by RXR tetramers may bring distant genomic regions into close physical proximity. As ligand-binding induces the dissociation of RXR tetramers into dimers, can alter gene expression by modulating DNA architecture. Here we show that inhibition of mammary carcinoma cell growth by RXR ligands stem from the ability of these compounds to regulate the oligomeric state of RXR and is independent of the direct intrinsic transcriptional activity of the receptor. The data suggest that compounds that trigger dissociation of RXR tetramers may comprise a novel class of anti-carcinogenic agents.
PMID: 20188110 [PubMed - as supplied by publisher]