ATF6调节ABCA1基因的表达  

ATF6 Up-regulates ABCA1 Expression

作　　者：李红玲[1] 朱敏佳[2] 党怀欣[2] 王保国[1] 朱毅[2] 

机构地区：[1]北京天坛医院麻醉科,北京100040 [2]北京大学医学部生理学与病理生理学系教育部分子心血管重点实验室,北京100083

出　　处：《中国生物化学与分子生物学报》2006年第10期799-805,共7页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金资助项目(30570713 ;30470631)~~

摘　　要：ATP结合盒转运蛋白A1(ATP-binding cassette transporter A1,ABCA1)是近年来发现的极其重要的脂质转运大分子膜蛋白,它可将过量胆固醇从细胞内向细胞外输送到载脂蛋白并包装成高密度脂蛋白(HDL),促进胆固醇的逆转运.初步研究转录因子ATF6对ABCA1的表达调控,结果发现,ATF6在人胚胎肾细胞HEK293内剂量依赖性地调节ABCA1基因转录及蛋白质表达.ATF6调节ABCA1与内质网应激信号通路无关.启动子序列缺失与突变分析表明,ATF6作用区位于ABCA1启动子上游-156^-928bp之间,可能需要E-box的参与,但不需要DR4元件.动物试验结果显示,用腺病毒在C57小鼠肝脏过表达ATF6,在mRNA水平上调ABCA1.本研究发现了ATF6新的功能以及调控ABCA1的新机制.ATP-binding cassette transporter A1 （ABCA1） is an important membrane transporter for cholesterol and lipids, it promotes overloaded cholesterol to efflux from ceils to ApoA-I and package into high-density lipoprotein, which process involved in revise cholesterol transfer. In this study, we found the effect of transcription factor ATF6 on ABCA1 regulation in HEK293 cells. The results showed that ATF6 up-regulated ABCA1 transcriptional activity and protein expression in a dose-dependent manner. This regulation of ABCA1 by ATF6 was not through ER stress regulatory pathway. The analysis of promoter deletion and different function domain mutation revealed that responsive region to ATF6 located on the up stream of ABCA1 promoter within - 156 to -928 and that the conserved E-box motif, but not DR4 motif, might be responsible for the ATF6- mediated ABCA1 promoter activation. Further, the in vivo study demonstrated that overexpression of ATF6（N） by adenovirus in the liver of C57 mice increased ABCA1 at mRNA levels, as well as ATF6 target gene. Thus, this study provides a novel function for ATF6 and the new mechanism of ABCA1 regulation.

关 键 词：ATF6 ABCA1 脂代谢 基因表达 转录调控 

分 类 号：Q291[生物学—细胞生物学] Q786