In the field of molecular biology, the pregnane X receptor (PXR), also known as the steroid and xenobiotic sensing nuclear receptor (SXR) or nuclear receptor subfamily 1, group I, member 2 (NR1I2) is a protein that in humans is encoded by the NR1I2 (nuclear Receptor subfamily 1, group I, member 2) gene.
PXR 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 substances from the body. PXR 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.
^Liao SK, Axelrad AA (March 1975). "Erythropoietin-independent erythroid colony formation in vitro by hemopoietic cells of mice infected with friend virus". Int. J. Cancer15 (3): 467–82. doi:10.1002/ijc.2910150313. PMID1140862.
^Synold TW, Dussault I, Forman BM (May 2001). "The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux". Nat. Med.7 (5): 584–90. doi:10.1038/87912. PMID11329060.
^Geick A, Eichelbaum M, Burk O (May 2001). "Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin". J. Biol. Chem.276 (18): 14581–7. doi:10.1074/jbc.M010173200. PMID11297522.
Watkins RE, Noble SM, Redinbo MR (2002). "Structural insights into the promiscuity and function of the human pregnane X receptor.". Current opinion in drug discovery & development5 (1): 150–8. PMID11865669.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.". Gene200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.
Dotzlaw H, Leygue E, Watson P, Murphy LC (1999). "The human orphan receptor PXR messenger RNA is expressed in both normal and neoplastic breast tissue.". Clin. Cancer Res.5 (8): 2103–7. PMID10473093.
Geick A, Eichelbaum M, Burk O (2001). "Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin.". J. Biol. Chem.276 (18): 14581–7. doi:10.1074/jbc.M010173200. PMID11297522.
Watkins RE, Wisely GB, Moore LB, et al. (2001). "The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity.". Science292 (5525): 2329–33. doi:10.1126/science.1060762. PMID11408620.
Zhang J, Kuehl P, Green ED, et al. (2001). "The human pregnane X receptor: genomic structure and identification and functional characterization of natural allelic variants.". Pharmacogenetics11 (7): 555–72. doi:10.1097/00008571-200110000-00003. PMID11668216.
Gonzalez MM, Carlberg C (2002). "Cross-repression, a functional consequence of the physical interaction of non-liganded nuclear receptors and POU domain transcription factors.". J. Biol. Chem.277 (21): 18501–9. doi:10.1074/jbc.M200205200. PMID11891224.
Takeshita A, Taguchi M, Koibuchi N, Ozawa Y (2002). "Putative role of the orphan nuclear receptor SXR (steroid and xenobiotic receptor) in the mechanism of CYP3A4 inhibition by xenobiotics.". J. Biol. Chem.277 (36): 32453–8. doi:10.1074/jbc.M111245200. PMID12072427.
Chang TK, Bandiera SM, Chen J (2003). "Constitutive androstane receptor and pregnane X receptor gene expression in human liver: interindividual variability and correlation with CYP2B6 mRNA levels.". Drug Metab. Dispos.31 (1): 7–10. doi:10.1124/dmd.31.1.7. PMID12485946.