Nuclear receptor PXR, transcriptional circuits and metabolic relevance

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1812

Review

Ihunnah, Chibueze A.^1,2  Jiang, Mengxi^1,2  Xie, Wen^1,2,3 

[1] Univ Pittsburgh, Ctr Pharmacogenet, Pittsburgh, PA 15261 USA

[2] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA

[3] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15261 USA

关键词: Nuclear receptor;    Gene regulation;    Xenobiotic receptor;    Xenobiotics;    Endobiotics;   

DOI  :  10.1016/j.bbadis.2011.01.014

来源: Elsevier

【 摘 要 】

The pregnane X receptor (PXR, NR1I2) is a ligand activated transcription factor that belongs to the nuclear hormone receptor (NR) superfamily. PXR is highly expressed in the liver and intestine, but low levels of expression have also been found in many other tissues. PXR plays an integral role in xenobiotic and endobiotic metabolism by regulating the expression of drug-metabolizing enzymes and transporters, as well as genes implicated in the metabolism of endobiotics. PXR exerts its transcriptional regulation by binding to its DNA response elements as a heterodimer with the retinoid X receptor (RXR) and recruitment of a host of coactivators. The biological and physiological implications of PXR activation are broad, ranging from drug metabolism and drug-drug interactions to the homeostasis of numerous endobiotics, such as glucose, lipids, steroids, bile acids, bilirubin, retinoic acid, and bone minerals. The purpose of this article is to provide an overview on the transcriptional circuits and metabolic relevance controlled by PXR. This article is part of a Special Issue entitled: Translating Nuclear Receptors from Health to Disease. (C) 2011 Elsevier B.V. All rights reserved.

【 授权许可】

Free