The Interface between Cell Signaling Pathways and Pregnane X Receptor
| Autor: | Gregory Ruddy, Megan Carney, Robert S Rogers, Kaushal Parimi, Nick D'Ambrosio, Dakota Sudbeck, Elijah Elliott, Kaitlin Stackable, Annemarie Parker, Parker G Howe, Thomas Osterholt, Jeff L. Staudinger, Venkata P Peddada, Lauren Martin, Phill D Vainer |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cell signaling
QH301-705.5 SUMO protein Context (language use) Review ubiquitination Models Biological digestive system pregnane X receptor Animals Humans cell signaling nuclear receptor xenobiotics Biology (General) acetylation Pregnane X receptor Mechanism (biology) Chemistry phosphorylation General Medicine digestive system diseases SUMOylation Cell biology PARylation Nuclear receptor Phosphorylation Signal transduction Protein Processing Post-Translational Signal Transduction |
| Zdroj: | Cells, Vol 10, Iss 3262, p 3262 (2021) Cells |
| ISSN: | 2073-4409 |
| Popis: | Highly expressed in the enterohepatic system, pregnane X receptor (PXR, NR1I2) is a well-characterized nuclear receptor (NR) that regulates the expression of genes in the liver and intestines that encode key drug metabolizing enzymes and drug transporter proteins in mammals. The net effect of PXR activation is to increase metabolism and clear drugs and xenobiotics from the body, producing a protective effect and mediating clinically significant drug interaction in patients on combination therapy. The complete understanding of PXR biology is thus important for the development of safe and effective therapeutic strategies. Furthermore, PXR activation is now known to specifically transrepress the inflammatory- and nutrient-signaling pathways of gene expression, thereby providing a mechanism for linking these signaling pathways together with enzymatic drug biotransformation pathways in the liver and intestines. Recent research efforts highlight numerous post-translational modifications (PTMs) which significantly influence the biological function of PXR. However, this thrust of research is still in its infancy. In the context of gene-environment interactions, we present a review of the recent literature that implicates PXR PTMs in regulating its clinically relevant biology. We also provide a discussion of how these PTMs likely interface with each other to respond to extracellular cues to appropriately modify PXR activity. |
| Databáze: | OpenAIRE |
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