Carnahan Virginia E, Redinbo Matthew R
Department of Biochemistry and Biophysics, and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, USA.
Curr Drug Metab. 2005 Aug;6(4):357-67. doi: 10.2174/1389200054633844.
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.
孕烷X受体（PXR）是配体调节转录因子核受体家族的成员。与许多以前的孤儿核受体一样，它包含DNA和配体结合结构域，并作为与RXRα的异二聚体与靶基因调控区域中的反应元件结合。然而，与绝大多数核受体不同的是，PXR对多种化学性质不同的外源性和内源性物质作出反应，调节药物和胆汁酸代谢核心基因的表达。我们综述了PXR在配体结合方面的混杂性的结构基础、其对转录共调节因子的募集、其高阶核受体复合物的潜在形成以及其对靶基因表达的控制。结构灵活性似乎是该受体适应大小和形状各异的配体能力的核心。我们还讨论了PXR在药物相互作用、癌症和胆汁淤积性肝病中的作用的临床意义。
