Abstract
Pregnane X receptor (PXR) is a member of the nuclear receptor (NR) superfamily of ligand-activated transcription factors and is activated by a huge variety of endobiotics and xenobiotics, including many clinical drugs. PXR plays key roles not only as a xenosensor in the regulation of both major phase I and II drug metabolism and transporters but also as a physiological sensor in the modulation of bile acid and cholesterol metabolism, glucose and lipid metabolism, and bone and endocrine homeostasis.
Post-translational modifications such as phosphorylation have been shown to modulate the activity of many NRs, including PXR, and constitute an important mechanism for crosstalk between signaling pathways and regulation of genes involved in both xenobiotic and endobiotic metabolism. In addition, microRNAs have recently been shown to constitute another level of PXR activity regulation.
The objective of this review is to comprehensively summarize current understanding of post-transcriptional and post-translational modifications of PXR in regulation of xenobiotic-metabolizing cytochrome P450 (CYP) genes, mainly in hepatic tissue. We also discuss the importance of PXR in crosstalk with cell signaling pathways, which at the level of transcription modify expression of genes associated with some physiological and pathological stages in the organs. Finally, we indicate that these PXR modifications may have important impacts on CYP-mediated biotransformation of some clinically used drugs.
Keywords: Cytochrome P450, gene regulation, induction, post-transcriptional, post-translational modification, pregnane X receptor, PXR.
Current Drug Metabolism
Title:Post-translational and Post-transcriptional Modifications of Pregnane X Receptor (PXR) in Regulation of the Cytochrome P450 Superfamily
Volume: 14 Issue: 10
Author(s): Tomas Smutny, Sridhar Mani and Petr Pavek
Affiliation:
Keywords: Cytochrome P450, gene regulation, induction, post-transcriptional, post-translational modification, pregnane X receptor, PXR.
Abstract: Pregnane X receptor (PXR) is a member of the nuclear receptor (NR) superfamily of ligand-activated transcription factors and is activated by a huge variety of endobiotics and xenobiotics, including many clinical drugs. PXR plays key roles not only as a xenosensor in the regulation of both major phase I and II drug metabolism and transporters but also as a physiological sensor in the modulation of bile acid and cholesterol metabolism, glucose and lipid metabolism, and bone and endocrine homeostasis.
Post-translational modifications such as phosphorylation have been shown to modulate the activity of many NRs, including PXR, and constitute an important mechanism for crosstalk between signaling pathways and regulation of genes involved in both xenobiotic and endobiotic metabolism. In addition, microRNAs have recently been shown to constitute another level of PXR activity regulation.
The objective of this review is to comprehensively summarize current understanding of post-transcriptional and post-translational modifications of PXR in regulation of xenobiotic-metabolizing cytochrome P450 (CYP) genes, mainly in hepatic tissue. We also discuss the importance of PXR in crosstalk with cell signaling pathways, which at the level of transcription modify expression of genes associated with some physiological and pathological stages in the organs. Finally, we indicate that these PXR modifications may have important impacts on CYP-mediated biotransformation of some clinically used drugs.
Export Options
About this article
Cite this article as:
Smutny Tomas, Mani Sridhar and Pavek Petr, Post-translational and Post-transcriptional Modifications of Pregnane X Receptor (PXR) in Regulation of the Cytochrome P450 Superfamily, Current Drug Metabolism 2013; 14 (10) . https://dx.doi.org/10.2174/1389200214666131211153307
DOI https://dx.doi.org/10.2174/1389200214666131211153307 |
Print ISSN 1389-2002 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5453 |
Call for Papers in Thematic Issues
Exploring oxidative stress and the anti-oxidant defense system in chronic diseases: therapeutic strategies and future perspective
Ageing is facilitated by oxidative stress (OS), which happens spontaneously. Several studies have demonstrated that OS over an extended period of time has a role in the emergence of several chronic illnesses. Diabetes, cancer, and heart disease are a few examples of these ailments. An imbalance between the body's antioxidants ...read more
Impact of brain tissue binding and plasma protein binding of drugs in DMPK
The impression of brain tissue binding (BTB) or plasma protein binding (PPB) in Drug Metabolism and Pharmacokinetics is critical to understanding the distribution, efficacy, and potential toxicity of drugs that target the central nervous system (CNS). BTB and high PPB influence the distribution of drugs in the body and their ...read more
Metabolism-mediated xenobiotic toxicity
Considering the potent modulation of biotransformation enzyme expression and activities by various therapeutic drugs and environmental chemicals, and the commonly combined exposure of humans to both drugs and the ever increasing environmental pollutants simultaneously, knowledge about the combined toxic effects by modulating biotransformation enzymes, such as P450s, UDP- glucuronosyltransferases, and ...read more
Safety evaluation of vaccine combination
Vaccine combination safety evaluation is a critical field within immunology and public health that focuses on assessing the safety and efficacy of combining different vaccines to maximize protection against various diseases while minimizing potential adverse effects. This process is significant because it ensures that vaccines can be administered together without ...read more
Related Journals
![Wayfinder Image](/images/wayfinder.jpg)
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Inflamm-Aging, Cytokines and Aging: State of the Art, New Hypotheses on the Role of Mitochondria and New Perspectives from Systems Biology
Current Pharmaceutical Design Long Term Complications in Pediatric Liver Transplant Recipients: What Every Pediatrician Should Know
Current Pediatric Reviews Cognitive Behavioral Therapy for Adolescents at Clinical High Risk for Psychosis
Adolescent Psychiatry Autophagy and Mitochondria in Obesity and Type 2 Diabetes
Current Diabetes Reviews Pharmacological Targets for the Inhibition of Neurogenic Inflammation
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Bariatric Surgery - Effects on Obesity and Related co-Morbidities
Current Diabetes Reviews Long Chain n-3 Polyunsaturated Fatty Acids in the Prevention of Allergic and Cardiovascular Disease
Current Pharmaceutical Design Antidiabetic Potential of Naturally Occurring Sesquiterpenes: A Review
Current Topics in Medicinal Chemistry AMPK As A Target in Rare Diseases
Current Drug Targets Bioartificial Pancreas: Drug Delivery through Islet Microencapsulation to Treat Diabetes
Recent Patents on Biomedical Engineering (Discontinued) New Strategies for Metabolic Support in Cancer
Current Nutrition & Food Science Psychosocial Stress, Emotions and Cytokine-Related Disorders
Recent Patents on Inflammation & Allergy Drug Discovery Apoptosis in Sepsis: Mechanisms, Clinical Impact and Potential Therapeutic Targets
Current Pharmaceutical Design Valproic Acid and Epilepsy: From Molecular Mechanisms to Clinical Evidences
Current Neuropharmacology Endothelial Dysfunction in Metabolic Diseases: Role of Oxidation and Possible Therapeutic Employment of N-acetylcysteine
Current Medicinal Chemistry The Pleiotropic Effects of PPARs on Vascular Cells and Angiogenesis: Implications for Tissue Engineering
Current Stem Cell Research & Therapy Mammalian Target of Rapamycin (mTOR) Signalling Pathway-A Potential Target for Cancer Intervention: A Short Overview
Current Molecular Pharmacology Ghrelin and the Brain-gut Axis as a Pharmacological Target for Appetite Control
Current Pharmaceutical Design Discovery of JANUVIA <sup>TM</sup> (Sitagliptin), a Selective Dipeptidyl Peptidase IV Inhibitor for the Treatment of Type2 Diabetes.
Current Topics in Medicinal Chemistry BAFFling Autoimmune Disorders and Helicobacter pylori Disease: The Interplay between BAFF and the Th17 Response
Clinical Immunology, Endocrine & Metabolic Drugs (Discontinued)