ArticleBiochemical pharmacology2014
Identification and characterization of phosphorylation sites within the pregnane X receptor protein.
Article in Biochemical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- Insights of direct and indirect regulation of PXR through phosphorylation in fatty liver disease.Molecular pharmacology · 2025Review
- Phenobarbital in Nuclear Receptor Activation: An Update.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Article
- Review
- Mutual interaction between gut microbiota and protein/amino acid metabolism for host mucosal immunity and health.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2021Review
- Phosphorylation Modulates the Coregulatory Protein Exchange of the Nuclear Receptor Pregnane X Receptor.The Journal of pharmacology and experimental therapeutics · 2020Article
- Drug discovery technologies to identify and characterize modulators of the pregnane X receptor and the constitutive androstane receptor.Drug discovery today · 2019Review
- Role of c-Jun-N-Terminal Kinase in Pregnane X Receptor-Mediated Induction of Human Cytochrome P4503A4 In Vitro.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- Differential Regulation of CYP3A4 and CYP3A5 and its Implication in Drug Discovery.Current drug metabolism · 2017Review
- Regulation of PXR and CAR by protein-protein interaction and signaling crosstalk.Expert opinion on drug metabolism & toxicology · 2016Review
- Mechanisms of xenobiotic receptor activation: Direct vs. indirect.Biochimica et biophysica acta · 2016Review
- A SUMO-acetyl switch in PXR biology.Biochimica et biophysica acta · 2016Article
- Small-molecule modulators of PXR and CAR.Biochimica et biophysica acta · 2016Review
- Acetylation of lysine 109 modulates pregnane X receptor DNA binding and transcriptional activity.Biochimica et biophysica acta · 2016Article
- Pregnane X Receptor and Cancer: Context-Specificity is Key.Nuclear receptor research · 2016Article
- Tryptophan 299 is a conserved residue of human pregnane X receptor critical for the functional consequence of ligand binding.Biochemical pharmacology · 2016Article
- Human pregnane X receptor compromises the function of p53 and promotes malignant transformation.Cell death discovery · 2016Article
- SUMOylation and Ubiquitylation Circuitry Controls Pregnane X Receptor Biology in Hepatocytes.Drug metabolism and disposition: the biological fate of chemicals · 2015Article
- Serine 350 of human pregnane X receptor is crucial for its heterodimerization with retinoid X receptor alpha and transactivation of target genes in vitro and in vivo.Biochemical pharmacology · 2015Article
- Mg2+/Mn2+-dependent phosphatase 1A is involved in regulating pregnane X receptor-mediated cytochrome p450 3A4 gene expression.Drug metabolism and disposition: the biological fate of chemicals · 2015Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Pregnane X receptor (PXR) is a xenobiotic sensor regulating the expression of genes involved in xenobiotic detoxification and elimination. Phosphorylation plays an important role in modulating PXR activity and several phosphorylation sites have been predicted and characterized in in vitro experiments. Although PXR has been shown to be a phosphoprotein in vivo, the exact residues that are phosphorylated remain elusive. Using mass spectrometry, we identified for the first time S114, T133/135, S167, and S200 residues that are phosphorylated in PXR following an in vitro kinase assay using cyclin-dependent kinase 2. We further found that the phosphorylation at S114, T133, and T135 occurred in PXR isolated from cells. We tested the phosphodeficient and phosphomimetic mutants corresponding to all the sites identified and determined that phosphorylation at S114 attenuates the transcriptional activity of PXR, consistent with the observation that the S114D mutant displayed reduced association with the PXR-targeted DNA response element. Phosphomimetic mutations at either T133 or T135 did not show a significant change in transcriptional activity however, the dual phosphomimetic mutant T133D/T135D displayed reduced transcriptional activity. Subcellular localization studies showed a varied distribution of the mutants suggesting that the regulation of PXR is much more complex than what we can observe by just overexpressing the mutants. Thus, our results provide the first direct evidence that PXR is phosphorylated at specific residues and suggest that further investigation is warranted to fully understand the regulation of PXR by phosphorylation.
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