PXR variants:the impact on drug metabolism and therapeutic responses

作     者：C.Trent Brewer Taosheng Chen 

作者机构：Department of Chemical Biology and TherapeuticsSt.Jude Children's Research Hospital Integrated Biomedical Sciences ProgramUniversity of Tennessee Health Science Center 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2016年第6卷第5期

页      面：441-449页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 100706[医学-药理学] 1001[医学-基础医学(可授医学、理学学位)] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by the American Lebanese Syrian Associated Charities (ALSAC),St.Jude Children0s Research Hospital the U.S. National Institutes of Health (Grants GM086415,GM110034,GM118041 and P30-CA21765) 

主　　题：Pregnane X receptor Transcript variants Drug metabolism Therapeutic responses Toxicity 

摘      要：The pregnane X receptor(PXR) plays an important and diverse role in mediating xenobiotic induction of drug-metabolizing enzymes and *** protein isoforms of PXR exist,and they have differential transcriptional activity upon target genes; transcript variants 3(PXR3) and 4(PXR4) do not induce target gene expression,whereas transcript variants 1(PXR1) and 2(PXR2) respond to agonist by activating target gene *** protein variants also display differences in protein–protein interactions; PXR1 interacts with p53,whereas PXR3 does ***,the transcript variants of PXR that encode these protein isoforms are differentially regulated by methylation and deletions in the respective promoters of the variants,and their expression differs in various human cancers and also in cancerous tissue compared to adjacent normal ***1 and PXR4 m RNA are downregulated by methylation in cancerous tissue and have divergent effects on cellular proliferation when ectopically *** detailed and comparative mechanistic studies are required to predict the effect of PXR transcript variant expression on carcinogenesis,therapeutic response,and the development of toxicity.