SREBP-1c mediates the retinoid-dependent increase in fatty acid synthase promoter activity in HepG2
SREBP-1c mediates the retinoid-dependent increase in fatty acid synthase promoter activity in HepG2
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DOI：
10.1016/j.febslet.2007.05.022
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发表时间：
2007-06-12
期刊：
影响因子：
3.5
通讯作者：
Schweizer, Michael
中科院分区：
文献类型：
--
作者：
Roder, Karim;Zhang, Lei;Schweizer, Michael
用全反式维甲酸（RA）处理HepG 2诱导脂肪酸合成酶（FAS）mRNA和蛋白的表达。转染显示FAS启动子对类维生素A X受体（RXR）有正响应，但对RA受体（RAR）激动剂无正响应。由于RXR单独能够介导FAS的RA应答，因此可以排除FAS启动子中存在经典的RA应答元件。NF-Y和SREBP-1的结合位点被证明是RA反应所必需的。暴露于全反式RA增加了FAS转录激活因子SREBP-1的mRNA和蛋白水平。显性负性形式的SREBP-1c的过表达减弱了RA依赖的启动子活性的增加。这些数据表明，RXR配体可以刺激脂肪生成基因的表达，仅通过诱导转录和切割膜结合的REBP-1c。(c)2007年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Treatment of HepG2 with all-trans retinoic acid (RA) induces expression of fatty acid synthase (FAS) mRNA and protein. Transfections show that the FAS promoter positively responds to retinoid X receptor (RXR) but not to RA receptor (RAR) agonists. Since RXR alone is capable of mediating the RA response of FAS, the existence of a classical RA-responsive element in the FAS promoter may be ruled out. Binding sites for NF-Y and SREBP-1 proved to be essential for the RA response. Exposure to all-trans RA increased mRNA and protein levels of SREBP-1, a transcriptional activator for FAS. Overexpression of a dominant-negative form of SREBP-1c diminished the RA-dependent increase in promoter activity. These data demonstrate that RXR ligands can stimulate the expression of a lipogenic gene solely by inducing transcription and cleavage of membrane-bound REBP-1c. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.