alexa Post-translational modification of pregnane x receptor.
Clinical Research

Clinical Research

Journal of Clinical Trials

Author(s): Staudinger JL, Xu C, Biswas A, Mani S

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Abstract Pregnane x receptor (PXR, NR1I2) was originally characterized as a broad spectrum entero-hepatic xenobiotic 'sensor' and master-regulator of drug inducible gene expression. A compelling description of ligand-mediated gene activation has been unveiled in the last decade that firmly establishes this receptor's central role in the metabolism and transport of xenobiotics in mammals. Interestingly, pharmacotherapy with potent PXR ligands produces several profound side effects including decreased capacities for gluconeogenesis, lipid metabolism, and inflammation; likely due to PXR-mediated repression of gene expression programs underlying these pivotal physiological functions. An integrated model is emerging that reveals a sophisticated interplay between ligand binding and the ubiquitylation, phosphorylation, SUMOylation, and acetylation status of this important nuclear receptor protein. These discoveries point to a key role for the post-translational modification of PXR in the selective suppression of gene expression, and open the door to the study of completely new modes of regulation of the biological activity of PXR. Copyright © 2011 Elsevier Ltd. All rights reserved.
This article was published in Pharmacol Res and referenced in Journal of Clinical Trials

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