Regulation of PXR Function by Coactivator and Corepressor Proteins: Ligand Binding Is Just the Beginning

The pregnane X receptor (PXR, <i>NR1I2</i>) is a nuclear receptor which exerts its regulatory function by heterodimerization with the retinoid-X-receptor α (RXRα, <i>NR2B1</i>) and binding to the promoter and enhancer regions of diverse target genes. PXR is involved in the re...

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Autores principales:	Juan Pablo Rigalli, Dirk Theile, Julie Nilles, Johanna Weiss
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	coactivator coregulator corepressor nuclear receptor pregnane X receptor Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a1554bc0021e43bca23c40e3b7c676fd
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spelling	oai:doaj.org-article:a1554bc0021e43bca23c40e3b7c676fd2021-11-25T17:11:52ZRegulation of PXR Function by Coactivator and Corepressor Proteins: Ligand Binding Is Just the Beginning10.3390/cells101131372073-4409https://doaj.org/article/a1554bc0021e43bca23c40e3b7c676fd2021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3137https://doaj.org/toc/2073-4409The pregnane X receptor (PXR, <i>NR1I2</i>) is a nuclear receptor which exerts its regulatory function by heterodimerization with the retinoid-X-receptor α (RXRα, <i>NR2B1</i>) and binding to the promoter and enhancer regions of diverse target genes. PXR is involved in the regulation of drug metabolism and excretion, metabolic and immunological functions and cancer pathogenesis. PXR activity is strongly regulated by the association with coactivator and corepressor proteins. Coactivator proteins exhibit histone acetyltransferase or histone methyltransferase activity or associate with proteins having one of these activities, thus promoting chromatin decondensation and activation of the gene expression. On the contrary, corepressor proteins promote histone deacetylation and therefore favor chromatin condensation and repression of the gene expression. Several studies pointed to clear cell- and ligand-specific differences in the activation of PXR. In this article, we will review the critical role of coactivator and corepressor proteins as molecular determinants of the specificity of PXR-mediated effects. As already known for other nuclear receptors, understanding the complex mechanism of PXR activation in each cell type and under particular physiological and pathophysiological conditions may lead to the development of selective modulators with therapeutic potential.Juan Pablo RigalliDirk TheileJulie NillesJohanna WeissMDPI AGarticlecoactivatorcoregulatorcorepressornuclear receptorpregnane X receptorBiology (General)QH301-705.5ENCells, Vol 10, Iss 3137, p 3137 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	coactivator coregulator corepressor nuclear receptor pregnane X receptor Biology (General) QH301-705.5
spellingShingle	coactivator coregulator corepressor nuclear receptor pregnane X receptor Biology (General) QH301-705.5 Juan Pablo Rigalli Dirk Theile Julie Nilles Johanna Weiss Regulation of PXR Function by Coactivator and Corepressor Proteins: Ligand Binding Is Just the Beginning
description	The pregnane X receptor (PXR, <i>NR1I2</i>) is a nuclear receptor which exerts its regulatory function by heterodimerization with the retinoid-X-receptor α (RXRα, <i>NR2B1</i>) and binding to the promoter and enhancer regions of diverse target genes. PXR is involved in the regulation of drug metabolism and excretion, metabolic and immunological functions and cancer pathogenesis. PXR activity is strongly regulated by the association with coactivator and corepressor proteins. Coactivator proteins exhibit histone acetyltransferase or histone methyltransferase activity or associate with proteins having one of these activities, thus promoting chromatin decondensation and activation of the gene expression. On the contrary, corepressor proteins promote histone deacetylation and therefore favor chromatin condensation and repression of the gene expression. Several studies pointed to clear cell- and ligand-specific differences in the activation of PXR. In this article, we will review the critical role of coactivator and corepressor proteins as molecular determinants of the specificity of PXR-mediated effects. As already known for other nuclear receptors, understanding the complex mechanism of PXR activation in each cell type and under particular physiological and pathophysiological conditions may lead to the development of selective modulators with therapeutic potential.
format	article
author	Juan Pablo Rigalli Dirk Theile Julie Nilles Johanna Weiss
author_facet	Juan Pablo Rigalli Dirk Theile Julie Nilles Johanna Weiss
author_sort	Juan Pablo Rigalli
title	Regulation of PXR Function by Coactivator and Corepressor Proteins: Ligand Binding Is Just the Beginning
title_short	Regulation of PXR Function by Coactivator and Corepressor Proteins: Ligand Binding Is Just the Beginning
title_full	Regulation of PXR Function by Coactivator and Corepressor Proteins: Ligand Binding Is Just the Beginning
title_fullStr	Regulation of PXR Function by Coactivator and Corepressor Proteins: Ligand Binding Is Just the Beginning
title_full_unstemmed	Regulation of PXR Function by Coactivator and Corepressor Proteins: Ligand Binding Is Just the Beginning
title_sort	regulation of pxr function by coactivator and corepressor proteins: ligand binding is just the beginning
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a1554bc0021e43bca23c40e3b7c676fd
work_keys_str_mv	AT juanpablorigalli regulationofpxrfunctionbycoactivatorandcorepressorproteinsligandbindingisjustthebeginning AT dirktheile regulationofpxrfunctionbycoactivatorandcorepressorproteinsligandbindingisjustthebeginning AT julienilles regulationofpxrfunctionbycoactivatorandcorepressorproteinsligandbindingisjustthebeginning AT johannaweiss regulationofpxrfunctionbycoactivatorandcorepressorproteinsligandbindingisjustthebeginning
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Regulation of PXR Function by Coactivator and Corepressor Proteins: Ligand Binding Is Just the Beginning

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