Related Experiment Video
Updated: Jun 3, 2026
10:51
Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
Post-translational modification of pregnane x receptor
Jeff L Staudinger1, Chenshu Xu, Arunima Biswas
1Pharmacology and Toxicology, University of Kansas, 1251 Wescoe Hall Dr., 5038a Malott Hall, Lawrence, KA 66045, USA. stauding@ku.edu
Pharmacological Research
|March 15, 2011
Summary
The pregnane X receptor (PXR) regulates drug metabolism but can cause side effects. Its activity is modulated by post-translational modifications, offering new regulatory insights.
Area of Science:
- Pharmacology
- Molecular Biology
- Biochemistry
Background:
- Pregnane X receptor (PXR) is a xenobiotic sensor controlling drug metabolism and transport.
- PXR activation by ligands is crucial for xenobiotic processing in mammals.
- PXR ligands can induce side effects by repressing essential physiological functions.
Purpose of the Study:
- To explore the role of PXR in regulating gluconeogenesis, lipid metabolism, and inflammation.
- To investigate the interplay between ligand binding and PXR post-translational modifications.
- To understand novel regulatory mechanisms of PXR biological activity.
Main Methods:
- Ligand-mediated gene activation studies.
- Analysis of PXR interactions with ubiquitylation, phosphorylation, SUMOylation, and acetylation.
- Investigating PXR-mediated gene expression repression.
Main Results:
- PXR plays a central role in xenobiotic metabolism and transport.
- Pharmacotherapy with PXR ligands can negatively impact metabolic and inflammatory pathways.
- Post-translational modifications of PXR are critical for selective gene expression suppression.
Conclusions:
- PXR's role extends beyond xenobiotic sensing to regulating key physiological processes.
- Post-translational modifications offer a sophisticated mechanism for PXR-mediated gene regulation.
- Further research into PXR modification could reveal new therapeutic strategies.
Related Concept Videos
01:45Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
01:31Transducer Mechanism: Nuclear Receptors
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
01:12GPCR Desensitization
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
01:31Regulation of the Unfolded Protein Response
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
01:26Protein Modifications in the RER
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.