The peroxisome proliferator response element of the gene encoding the peroxisomal β-oxidation enzyme enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase is a target for constitutive androstane receptor β/9-<i>cis</i>-retinoic acid receptor-mediated transactivation

作     者：Kassam, A Winrow, CJ Fernandez-Rachubinski, F Capone, JP Rachubinski, RA 

作者机构：Univ Alberta Dept Cell Biol Edmonton AB T6G 2H7 Canada Univ Alberta Dept Biochem Edmonton AB T6G 2H7 Canada McMaster Univ Dept Biochem Hamilton ON L8N 3Z5 Canada 

出 版 物：《JOURNAL OF BIOLOGICAL CHEMISTRY》 (J. Biol. Chem.)

年 卷 期：2000年第275卷第6期

页      面：4345-4350页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 1001[医学-基础医学(可授医学、理学学位)] 07[理学] 100101[医学-人体解剖与组织胚胎学] 100102[医学-免疫学] 071007[理学-遗传学] 10[医学] 

主　　题：酰基CoA氧化酶 雄甾烷醇类/药理学 结合 竞争性 细胞系 DNA结合蛋白质类/遗传学 二聚作用 烯酰CoA水合酶/遗传学 基因表达调控 酶学 氧化还原酶类/遗传学 过氧化酶体激增剂/药理学 过氧化物酶体类/酶学 过氧化物酶体类/遗传学 嘧啶类/药理学 受体 胞质和核/遗传学 受体 维甲酸/代谢 调控序列 核酸/遗传学 维甲类X受体 转录因子/遗传学 转录因子/代谢 转录激活/遗传学 动物 人类 大鼠 

摘      要：The genes encoding the first two enzymes of the peroxisomal beta-oxidation pathway, acyl-CoA oxidase (AOx) and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (HD), contain upstream cis-acting regulatory regions termed peroxisome proliferator response elements (PPRE), Transcription of these genes is mediated through the binding of peroxisome proliferator-activated receptor or (PPAR alpha), which binds to a PPRE as a heterodimer with the 9-cis-retinoic acid receptor (RXR alpha). Here we demonstrate that the HD-PPRE is also a target for the constitutive androstane receptor beta (CAR beta) In vitro binding analysis showed that CAR beta bound the HD-PPRE, but not the AOx-PPRE, as a heterodimer with RXR alpha, Binding of CAR beta/RXR alpha to the HD-PPRE occurred via determinants that overlap partially with those required for PPAR alpha/RXR alpha binding. In vivo, CAR beta/RXR alpha activated transcription from an HD-PPRE luciferase reporter construct, Interestingly, CAR beta was shown to also modulate PPAR alpha/RXR alpha-mediated transactivation in a response element-specific manner. In the presence of the peroxisome proliferator, Wy-14,643, CAR beta had no effect on PPAR alpha/RXR alpha-mediated transactivation from the HD-PPRE but antagonized transactivation from the AOx-PPRE in both the presence and the absence of proliferator, Our results illustrate that transcription of the AOx and HD genes is differentially regulated by CAR beta and that the HD gene is a specific target for regulation by CAR beta, Overall, this study proposes a novel role for CAR beta in the regulation of peroxisomal beta-oxidation.