Role of CAR and PXR in xenobiotic sensing and metabolism.

Expert Opinion on Drug Metabolism & Toxicology
Yue-Ming WangTaosheng Chen

Abstract

The xenobiotic detoxification system, which protects the human body from external chemicals, comprises drug-metabolizing enzymes and transporters whose expressions are regulated by pregnane X receptor (PXR) and the constitutive androstane receptor (CAR). The progress made in a large number of recent studies calls for a timely review to summarize and highlight these key discoveries. This review summarizes recent advances in elucidating the roles of PXR and CAR in the xenobiotic detoxification system. It also highlights the progress in understanding the regulation of PXR and CAR activity at the post-translational levels, as well as the structural basis for the regulation of these two xenobiotic sensors. Future efforts are needed to discover novel agonists and antagonists with species and isoform selectivity, to systematically understand the regulation of PXR and CAR at multiple levels (transcriptional, post-transcriptional and post-translational levels) in response to xenobiotics exposure, and to solve the structures of the full-length receptors, which will be enabled by improved protein expression and purification techniques and approaches. In addition, more efforts will be needed to validate PXR and CAR as disease-related thera...Continue Reading

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