Pregnane X receptor

Pregnane X receptor

In the field of molecular biology, the pregnane X receptor (PXR), also known as NR1I2 (nuclear receptor subfamily 1, group I, member 2), is a nuclear receptor whose primary function is to sense the presence of foreign toxic substances and in response up regulate the expression of proteins involved in the detoxification and clearance of these substance from the body.

PXR is encoded by the gene. The product of this gene belongs to the nuclear receptor superfamily, members of which are transcription factors characterized by a ligand-binding domain and a DNA-binding domain. The encoded protein is a transcriptional regulator of the cytochrome P450 gene CYP3A4, binding to the response element of the CYP3A4 promoter as a heterodimer with the 9-cis retinoic acid receptor RXR. It is activated by a range of compounds that induce CYP3A4, including dexamethasone and rifampicin. Several alternatively spliced transcripts encoding different isoforms, some of which use non-AUG (CUG) translation initiation codon, have been described for this gene. Additional transcript variants exist, however, they have not been fully characterized.

Activation

PXR is activated by a large number of endogenous and exogenous chemicals including steroids, antibiotics, antimycotics, bile acids, and hyperforin, a constituent of the herbal antidepressant St. John's Wort.

Function

Like other type II nuclear receptors, when activated, it forms a heterodimer with the retinoid X receptor, and binds to hormone response elements on DNA which elicits expression of gene products.

One of the primary targets of PXR activation is the induction of CYP3A4, an important phase I oxidative enzyme that is responsible for the metabolism of many drugs.

In addition, PXR up regulates the expression of phase II conjugating enzymes such as glutathione S-transferase and phase III transport uptake and efflux proteins such as OATP2 and MDR1 ().

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