ArticleBiochimica et biophysica acta2016
Acetylation of lysine 109 modulates pregnane X receptor DNA binding and transcriptional activity.
Article in Biochimica et biophysica acta, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Dose-dependent induction of CYP3A activity by St. John's wort alone and in combination with rifampin.Clinical and translational science · 2024Article
- S-nitrosylation attenuates pregnane X receptor hyperactivity and acetaminophen-induced liver injury.JCI insight · 2024Article
- Article
- Insights into the critical role of the PXR in preventing carcinogenesis and chemotherapeutic drug resistance.International journal of biological sciences · 2022Review
- Discrepancy in interactions and conformational dynamics of pregnane X receptor (PXR) bound to an agonist and a novel competitive antagonist.Computational and structural biotechnology journal · 2022Article
- Review
- Regulation of PXR Function by Coactivator and Corepressor Proteins: Ligand Binding Is Just the Beginning.Cells · 2021Review
- Phosphorylation Modulates the Coregulatory Protein Exchange of the Nuclear Receptor Pregnane X Receptor.The Journal of pharmacology and experimental therapeutics · 2020Article
- PXR: a center of transcriptional regulation in cancer.Acta pharmaceutica Sinica. B · 2020Review
- Nutritional status modifies pregnane X receptor regulated transcriptome.Scientific reports · 2019Article
- Novel complex of HAT protein TIP60 and nuclear receptor PXR promotes cell migration and adhesion.Scientific reports · 2017Article
- Fine tuning of vitamin D receptor (VDR) activity by post-transcriptional and post-translational modifications.Oncotarget · 2017Review
- Regulation of PXR and CAR by protein-protein interaction and signaling crosstalk.Expert opinion on drug metabolism & toxicology · 2016Review
- Regulation of PXR in drug metabolism: chemical and structural perspectives.Expert opinion on drug metabolism & toxicologyReview
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Pregnane X receptor (PXR) is a major transcriptional regulator of xenobiotic metabolism and transport pathways in the liver and intestines, which are critical for protecting organisms against potentially harmful xenobiotic and endobiotic compounds. Inadvertent activation of drug metabolism pathways through PXR is known to contribute to drug resistance, adverse drug-drug interactions, and drug toxicity in humans. In both humans and rodents, PXR has been implicated in non-alcoholic fatty liver disease, diabetes, obesity, inflammatory bowel disease, and cancer. Because of PXR's important functions, it has been a therapeutic target of interest for a long time. More recent mechanistic studies have shown that PXR is modulated by multiple PTMs. Herein we provide the first investigation of the role of acetylation in modulating PXR activity. Through LC-MS/MS analysis, we identified lysine 109 (K109) in the hinge as PXR's major acetylation site. Using various biochemical and cell-based assays, we show that PXR's acetylation status and transcriptional activity are modulated by E1A binding protein (p300) and sirtuin 1 (SIRT1). Based on analysis of acetylation site mutants, we found that acetylation at K109 represses PXR transcriptional activity. The mechanism involves loss of RXRα dimerization and reduced binding to cognate DNA response elements. This mechanism may represent a promising therapeutic target using modulators of PXR acetylation levels. This article is part of a Special Issue entitled: Xenobiotic nuclear receptors: New Tricks for An Old Dog, edited by Dr. Wen Xie.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.