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- Title
Characterization of the human IDH1 gene promoter.
- Authors
Yutaka Takihara; Ryuji Otani; Takuro Ishii; Shunsuke Takaoka; Yuki Nakano; Kaori Inoue; Larsen, Steven; Yoko Ogino; Masashi Asai; Sei-ichi Tanuma; Fumiaki Uchiumi
- 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, transresveratrol (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.
- Subjects
RESVERATROL; NAD (Coenzyme); NICOTINAMIDE adenine dinucleotide phosphate; HUMAN genes; ISOCITRATE dehydrogenase; GENE expression; TRICARBOXYLIC acids
- Publication
AIMS Molecular Science, 2023, Vol 10, Issue 3, p186
- ISSN
2372-028X
- Publication type
Article
- DOI
10.3934/molsci.2023013