Mackowiak Bryan, Wang Hongbing
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 Penn Street, Baltimore, MD 21201, United States.
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 Penn Street, Baltimore, MD 21201, United States.
Biochim Biophys Acta. 2016 Sep;1859(9):1130-1140. doi: 10.1016/j.bbagrm.2016.02.006. Epub 2016 Feb 10.
The so-called xenobiotic receptors (XRs) have functionally evolved into cellular sensors for both endogenous and exogenous stimuli by regulating the transcription of genes encoding drug-metabolizing enzymes and transporters, as well as those involving energy homeostasis, cell proliferation, and/or immune responses. Unlike prototypical steroid hormone receptors, XRs are activated through both direct ligand-binding and ligand-independent (indirect) mechanisms by a plethora of structurally unrelated chemicals. This review covers research literature that discusses direct vs. indirect activation of XRs. A particular focus is centered on the signaling control of the constitutive androstane receptor (CAR), the pregnane X receptor (PXR), and the aryl hydrocarbon receptor (AhR). We expect that this review will shed light on both the common and distinct mechanisms associated with activation of these three XRs. This article is part of a Special Issue entitled: Xenobiotic nuclear receptors: New Tricks for An Old Dog, edited by Dr. Wen Xie.
所谓的异源物受体（XRs）已在功能上进化为细胞传感器，通过调节编码药物代谢酶和转运蛋白的基因转录，以及涉及能量稳态、细胞增殖和/或免疫反应的基因转录，来感知内源性和外源性刺激。与典型的类固醇激素受体不同，XRs可通过直接配体结合和配体非依赖性（间接）机制，被大量结构不相关的化学物质激活。本综述涵盖了讨论XRs直接激活与间接激活的研究文献。特别关注的是组成型雄甾烷受体（CAR）、孕烷X受体（PXR）和芳烃受体（AhR）的信号控制。我们期望本综述能阐明与这三种XRs激活相关的共同机制和独特机制。本文是名为《异源物核受体：老狗学新招》特刊的一部分，由谢文博士编辑。
