論文 - 詳細
| RRC ID | 38276 |
|---|---|
| 著者 | Yamazaki T, Ohmi A, Kurumaya H, Kato K, Abe T, Yamamoto H, Nakanishi N, Okuyama R, Umemura M, Kaise T, Watanabe R, Okawa Y, Takahashi S, Takahashi Y. |
| タイトル | Regulation of the human CHOP gene promoter by the stress response transcription factor ATF5 via the AARE1 site in human hepatoma HepG2 cells. |
| ジャーナル | Life Sci |
| Abstract |
AIMS:Activating transcription factor (ATF) 5 is a member of the cAMP response element-binding protein (CREB)/ATF family of transcription factors. We have shown that ATF5 is a stress response transcription factor that responds to amino acid limitation, arsenite exposure, or cadmium exposure. In this study we investigated whether ATF5 is involved in the regulation of CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) gene expression. MAIN METHODS:We used a transient transfection system to express ATF5 and analyzed the regulation of CHOP gene promoter in human hepatoma, HepG2 cells. We also studied the effect of ATF5 knockdown on arsenite-induced CHOP protein expression and arsenite-induced cell death of HepG2 cells. KEY FINDINGS:We showed that ATF5 activates the CHOP gene promoter in HepG2 cells. Both deletion analysis and point mutations of the promoter revealed that amino acid response element (AARE) 1 is responsible for ATF5-dependent promoter activation. Furthermore, the existence of either AARE1 or activating protein-1 (AP-1) site is sufficient for transcriptional activation of the CHOP gene promoter by arsenite exposure, although complete induction requires the existence of both elements. We also demonstrated that knockdown of ATF5 reduced arsenite-induced CHOP protein expression and arsenite-induced cell death of HepG2 cells. SIGNIFICANCE:These results suggested that the CHOP gene is a potential target for ATF5, and that ATF5 raises the arsenite-induced CHOP gene expression level via the AARE1 site in HepG2 cells. |
| 巻・号 | 87(9-10) |
| ページ | 294-301 |
| 公開日 | 2010-8-28 |
| DOI | 10.1016/j.lfs.2010.07.006 |
| PII | S0024-3205(10)00293-6 |
| PMID | 20654631 |
| MeSH | Activating Transcription Factors / antagonists & inhibitors Activating Transcription Factors / genetics Activating Transcription Factors / physiology* Amino Acids / pharmacology* Apoptosis / drug effects Arsenites / pharmacology Binding Sites Blotting, Western Cell Survival / drug effects Cloning, Molecular Dose-Response Relationship, Drug Gene Deletion Gene Expression Regulation, Neoplastic* / drug effects HeLa Cells Hep G2 Cells Humans Luciferases / genetics Plasmids Point Mutation Promoter Regions, Genetic RNA, Small Interfering / pharmacology Response Elements / genetics* Sodium Compounds / pharmacology Transcription Factor AP-1 / genetics Transcription Factor CHOP / genetics* Transfection Up-Regulation |
| IF | 3.647 |
| 引用数 | 16 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL PHARMACOLOGY & PHARMACY |
| リソース情報 | |
| ヒト・動物細胞 | |