The Interface between Cell Signaling Pathways and Pregnane X Receptor

Highly expressed in the enterohepatic system, pregnane X receptor (PXR, NR1I2) is a well-characterized nuclear receptor (NR) that regulates the expression of genes in the liver and intestines that encode key drug metabolizing enzymes and drug transporter proteins in mammals. The net effect of PXR ac...

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Autores principales:	Robert S. Rogers, Annemarie Parker, Phill D. Vainer, Elijah Elliott, Dakota Sudbeck, Kaushal Parimi, Venkata P. Peddada, Parker G. Howe, Nick D’Ambrosio, Gregory Ruddy, Kaitlin Stackable, Megan Carney, Lauren Martin, Thomas Osterholt, Jeff L. Staudinger
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	nuclear receptor pregnane X receptor xenobiotics cell signaling phosphorylation SUMOylation Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/12300440a91a4307ae823bbd7287c260
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spelling	oai:doaj.org-article:12300440a91a4307ae823bbd7287c2602021-11-25T17:13:25ZThe Interface between Cell Signaling Pathways and Pregnane X Receptor10.3390/cells101132622073-4409https://doaj.org/article/12300440a91a4307ae823bbd7287c2602021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3262https://doaj.org/toc/2073-4409Highly expressed in the enterohepatic system, pregnane X receptor (PXR, NR1I2) is a well-characterized nuclear receptor (NR) that regulates the expression of genes in the liver and intestines that encode key drug metabolizing enzymes and drug transporter proteins in mammals. The net effect of PXR activation is to increase metabolism and clear drugs and xenobiotics from the body, producing a protective effect and mediating clinically significant drug interaction in patients on combination therapy. The complete understanding of PXR biology is thus important for the development of safe and effective therapeutic strategies. Furthermore, PXR activation is now known to specifically transrepress the inflammatory- and nutrient-signaling pathways of gene expression, thereby providing a mechanism for linking these signaling pathways together with enzymatic drug biotransformation pathways in the liver and intestines. Recent research efforts highlight numerous post-translational modifications (PTMs) which significantly influence the biological function of PXR. However, this thrust of research is still in its infancy. In the context of gene-environment interactions, we present a review of the recent literature that implicates PXR PTMs in regulating its clinically relevant biology. We also provide a discussion of how these PTMs likely interface with each other to respond to extracellular cues to appropriately modify PXR activity.Robert S. RogersAnnemarie ParkerPhill D. VainerElijah ElliottDakota SudbeckKaushal ParimiVenkata P. PeddadaParker G. HoweNick D’AmbrosioGregory RuddyKaitlin StackableMegan CarneyLauren MartinThomas OsterholtJeff L. StaudingerMDPI AGarticlenuclear receptorpregnane X receptorxenobioticscell signalingphosphorylationSUMOylationBiology (General)QH301-705.5ENCells, Vol 10, Iss 3262, p 3262 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	nuclear receptor pregnane X receptor xenobiotics cell signaling phosphorylation SUMOylation Biology (General) QH301-705.5
spellingShingle	nuclear receptor pregnane X receptor xenobiotics cell signaling phosphorylation SUMOylation Biology (General) QH301-705.5 Robert S. Rogers Annemarie Parker Phill D. Vainer Elijah Elliott Dakota Sudbeck Kaushal Parimi Venkata P. Peddada Parker G. Howe Nick D’Ambrosio Gregory Ruddy Kaitlin Stackable Megan Carney Lauren Martin Thomas Osterholt Jeff L. Staudinger The Interface between Cell Signaling Pathways and Pregnane X Receptor
description	Highly expressed in the enterohepatic system, pregnane X receptor (PXR, NR1I2) is a well-characterized nuclear receptor (NR) that regulates the expression of genes in the liver and intestines that encode key drug metabolizing enzymes and drug transporter proteins in mammals. The net effect of PXR activation is to increase metabolism and clear drugs and xenobiotics from the body, producing a protective effect and mediating clinically significant drug interaction in patients on combination therapy. The complete understanding of PXR biology is thus important for the development of safe and effective therapeutic strategies. Furthermore, PXR activation is now known to specifically transrepress the inflammatory- and nutrient-signaling pathways of gene expression, thereby providing a mechanism for linking these signaling pathways together with enzymatic drug biotransformation pathways in the liver and intestines. Recent research efforts highlight numerous post-translational modifications (PTMs) which significantly influence the biological function of PXR. However, this thrust of research is still in its infancy. In the context of gene-environment interactions, we present a review of the recent literature that implicates PXR PTMs in regulating its clinically relevant biology. We also provide a discussion of how these PTMs likely interface with each other to respond to extracellular cues to appropriately modify PXR activity.
format	article
author	Robert S. Rogers Annemarie Parker Phill D. Vainer Elijah Elliott Dakota Sudbeck Kaushal Parimi Venkata P. Peddada Parker G. Howe Nick D’Ambrosio Gregory Ruddy Kaitlin Stackable Megan Carney Lauren Martin Thomas Osterholt Jeff L. Staudinger
author_facet	Robert S. Rogers Annemarie Parker Phill D. Vainer Elijah Elliott Dakota Sudbeck Kaushal Parimi Venkata P. Peddada Parker G. Howe Nick D’Ambrosio Gregory Ruddy Kaitlin Stackable Megan Carney Lauren Martin Thomas Osterholt Jeff L. Staudinger
author_sort	Robert S. Rogers
title	The Interface between Cell Signaling Pathways and Pregnane X Receptor
title_short	The Interface between Cell Signaling Pathways and Pregnane X Receptor
title_full	The Interface between Cell Signaling Pathways and Pregnane X Receptor
title_fullStr	The Interface between Cell Signaling Pathways and Pregnane X Receptor
title_full_unstemmed	The Interface between Cell Signaling Pathways and Pregnane X Receptor
title_sort	interface between cell signaling pathways and pregnane x receptor
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/12300440a91a4307ae823bbd7287c260
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The Interface between Cell Signaling Pathways and Pregnane X Receptor

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