Characterization of the human IDH1 gene promoter

IF 0.7 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Y. Takihara, Ryuji Otani, T. Ishii, Shunsuke Takaoka, Yuki Nakano, Kaori Inoue, S. Larsen, Yoko Ogino, Masashi Asai, S. Tanuma, F. Uchiumi
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引用次数: 0

Abstract

In cancer, the production of ATP depends mainly on glycolysis, usually accompanied by the dysfunction of the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS). Nicotinamide adenine dinucleotide (NAD+) is a coenzyme for various biological enzymatic reactions such as those involved in the TCA cycle. To investigate the molecular mechanisms involved in carcinogenesis, the transcription system of genes associated with mitochondrial function should be elucidated. In this study, we isolated several mitochondrial function-associated bidirectional promoters and tested whether they responded to NAD+-metabolism regulating compounds, namely, trans-resveratrol (Rsv), 2-deoxy-D-glucose (2DG), 3-amino benzamide (3AB), and olaparib (OLA), in HeLa S3 cells. Transient transfection and luciferase (Luc) reporter assay showed that the IDH1 promoter was prominently activated by these compounds. The IDH1 gene, which encodes a nicotinamide adenine dinucleotide phosphate (NADP+) dependent isocitrate dehydrogenase, is frequently mutated in glioma and leukemia cells. In this study, RT-PCR showed that IDH1 gene and protein expression was induced in response to the NAD+-regulating drugs Rsv and 3AB. However, IDH1 protein amount was rather stable at control level. The result suggested that a post-transcriptional controlling system works to keep IDH1 at a stable level.
人IDH1基因启动子的鉴定
在癌症中,ATP的产生主要依赖于糖酵解,通常伴随着三羧酸(TCA)循环和氧化磷酸化(OXPHOS)的功能障碍。烟酰胺腺嘌呤二核苷酸(NAD+)是多种生物酶反应的辅酶,如参与TCA循环的反应。为了研究癌变的分子机制,需要阐明与线粒体功能相关的基因转录系统。在这项研究中,我们分离了几个线粒体功能相关的双向启动子,并测试了它们是否对HeLa S3细胞中NAD+代谢调节化合物,即反式白藜芦醇(Rsv)、2-脱氧-d -葡萄糖(2DG)、3-氨基苯酰胺(3AB)和奥拉帕尼(OLA)有反应。瞬时转染和荧光素酶(Luc)报告基因检测表明,这些化合物显著激活了IDH1启动子。编码烟酰胺腺嘌呤二核苷酸磷酸(NADP+)依赖性异柠檬酸脱氢酶的IDH1基因在胶质瘤和白血病细胞中经常发生突变。本研究通过RT-PCR检测发现,NAD+调节药物Rsv和3AB诱导了IDH1基因和蛋白的表达。而IDH1蛋白量在对照水平下较为稳定。结果表明,一个转录后控制系统使IDH1保持在稳定的水平。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
AIMS Molecular Science
AIMS Molecular Science BIOCHEMISTRY & MOLECULAR BIOLOGY-
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4
审稿时长
5 weeks
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