Biomaterial Database

Structure and function of the human nuclear xenobiotic receptor PXR. 2005

Virginia E Carnahan, and Matthew R Redinbo

Department of Biochemistry and Biophysics, and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, USA.

The pregnane X receptor (PXR) is a member of the nuclear receptor family of ligand-regulated transcription factors. Like many former orphan nuclear receptors, it contains both DNA and ligand binding domains and binds to response elements in the regulatory regions of target genes as a heterodimer with RXRalpha. Unlike the vast majority of nuclear receptors, however, PXR responds to a wide variety of chemically distinct xenobiotics and endobiotics, regulating the expression of genes central to both drug and bile acid metabolism. We review the structural basis of PXR's promiscuity in ligand binding, its recruitment of transcriptional coregulators, its potential formation of higher-order nuclear receptor complexes, and its control of target gene expression. Structural flexibility appears to be central to the receptor's ability to conform to ligands that differ both in size and shape. We also discuss the clinical implications of PXR's role in the drug-drug interactions, cancer, and cholestatic liver disease.

UI	MeSH Term	Description	Entries
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D011987	Receptors, Steroid	Proteins found usually in the cytoplasm or nucleus that specifically bind steroid hormones and trigger changes influencing the behavior of cells. The steroid receptor-steroid hormone complex regulates the transcription of specific genes.	Corticosteroid Receptors,Receptors, Corticosteroid,Steroid Receptors,Corticosteroid Receptor,Receptors, Steroids,Steroid Receptor,Receptor, Corticosteroid,Receptor, Steroid,Steroids Receptors
D004247	DNA	A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004347	Drug Interactions	The action of a drug that may affect the activity, metabolism, or toxicity of another drug.	Drug Interaction,Interaction, Drug,Interactions, Drug
D004358	Drug Therapy	The use of DRUGS to treat a DISEASE or its symptoms. One example is the use of ANTINEOPLASTIC AGENTS to treat CANCER.	Chemotherapy,Pharmacotherapy,Therapy, Drug,Chemotherapies,Drug Therapies,Pharmacotherapies,Therapies, Drug
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077297	Pregnane X Receptor	Steroid receptor that binds and is activated by variety of endogenous compounds and XENOBIOTICS. It binds the response element in promoters of genes that encode CYTOCHROME P450 3A4 and ATP BINDING CASSETTE TRANSPORTER, SUBFAMILY B, MEMBER 1 proteins, and also activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs, and endogenous compounds. It is activated by the antibiotic RIFAMPICIN and various plant metabolites, such as hyperforin, guggulipid, colupulone, and ISOFLAVONES.	NR1I2,Nuclear Receptor Subfamily 1, Group I, Member 2,SXR Receptor,Steroid X Receptor,Steroid and Xenobiotic Receptor
D015262	Xenobiotics	Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc.	Xenobiotic
D018160	Receptors, Cytoplasmic and Nuclear	Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS.	Cytoplasmic Receptor,Cytoplasmic and Nuclear Receptors,Cytosolic and Nuclear Receptors,Hormone Receptors, Cytoplasmic,Hormone Receptors, Nuclear,Nuclear Hormone Receptor,Nuclear Receptor,Nuclear and Cytoplasmic Receptors,Cytoplasmic Hormone Receptors,Cytoplasmic Receptors,Cytosol and Nuclear Receptors,Intracellular Membrane Receptors,Nuclear Hormone Receptors,Nuclear Receptors,Receptors, Cytoplasmic,Receptors, Cytosol and Nuclear,Receptors, Cytosolic and Nuclear,Receptors, Intracellular Membrane,Receptors, Nuclear,Receptors, Nuclear and Cytoplasmic,Hormone Receptor, Nuclear,Membrane Receptors, Intracellular,Receptor, Cytoplasmic,Receptor, Nuclear,Receptor, Nuclear Hormone,Receptors, Cytoplasmic Hormone,Receptors, Nuclear Hormone