Signaling control of the constitutive androstane receptor （CAR）

作     者：Hui Yang Hongbing Wang 

作者机构：Department of Pharmaceutical Sciences University of Maryland School of Pharmacy 20 Penn Street Baltimore MD 21201 USA 

出 版 物：《Protein & Cell》 (蛋白质与细胞（英文版）)

年 卷 期：2014年第5卷第2期

页      面：113-123页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学] 071009[理学-细胞生物学] 09[农学] 0901[农学-作物学] 090102[农学-作物遗传育种] 

基　　金：National Institutes of Health, (DK061652) National Institute of General Medical Sciences, NIGMS, (R01GM107058) 

主　　题：constitutive androstane receptor nucleartranslocation phosphorylation signaling regulation 

摘      要：The constitutive androstane receptor （CAR, NRll3） plays a crucial role in the regulation of drug metabolism, energy homeostasis, and cancer development through modulating the transcription of its numerous target genes. Different from prototypical nuclear receptors, CAR can be activated by either direct ligand binding or ligand-independent （indirect） mechanisms both initiated with nuclear translocation of CAR from the cytoplasm. In comparison to the well-defined ligand-based activation, indirect activation of CAR appears to be exclusively involved in the nuclear translocation through mecha- nisms yet to be fully understood. Accumulating evi- dence reveals that without activation, CAR forms a protein complex in the cytoplasm where it can be func- tionally affected by multiple signaling pathways. In this review, we discuss recent progresses in our under- standing of the signaling regulation of CAR nuclear accumulation and activation. We expect that this review will also provide greater insight into the similarity and difference between the mechanisms of direct vs. indirect human CAR activation.