論文 - 詳細
| RRC ID | 41639 |
|---|---|
| 著者 | Furukawa Y, Nishimura N, Furukawa Y, Satoh M, Endo H, Iwase S, Yamada H, Matsuda M, Kano Y, Nakamura M. |
| タイトル | Apaf-1 is a mediator of E2F-1-induced apoptosis. |
| ジャーナル | J Biol Chem |
| Abstract |
E2F-1 is capable of promoting both cell cycle progression and apoptosis. The latter is important for suppressing untoward expansion of proliferating cells. In this study, we investigated its underlying mechanisms. E2F-1-induced apoptosis was accompanied by caspase-9 activation and inhibited by a specific inhibitor of caspase-9 in K562 sublines overexpressing E2F-1. E2F-1 enhanced the expression of Apaf-1 without the cytosolic accumulation of cytochrome c. Apaf-1-deficient melanoma cell lines were resistant to E2F-1, indicating that Apaf-1 is an essential element of E2F-1-mediated apoptosis. Finally, we isolated the promoter region of the Apaf-1 gene and found a putative binding site for E2F. A chromatin immunoprecipitation assay revealed that E2F-1 bound to Apaf-1 promoter upon E2F-1 overexpression, suggesting that Apaf-1 is under transcriptional regulation of E2F-1. These data demonstrate a novel mechanism of apoptosis in which an increase in Apaf-1 levels results in direct activation of caspase-9 without mitochondrial damage, leading to the initiation of a caspase cascade. |
| 巻・号 | 277(42) |
| ページ | 39760-8 |
| 公開日 | 2002-10-18 |
| DOI | 10.1074/jbc.M200805200 |
| PII | S0021-9258(19)72343-6 |
| PMID | 12149244 |
| MeSH | Apoptosis* Apoptotic Protease-Activating Factor 1 Base Sequence Binding Sites Blotting, Northern Caspase 3 Caspase 6 Caspase 9 Caspases / metabolism Cell Cycle Proteins* Cell Line Chromatin / metabolism CpG Islands Cytosol / metabolism DNA-Binding Proteins* E2F Transcription Factors E2F1 Transcription Factor Enzyme Activation Flow Cytometry Gene Expression Regulation Humans Immunoblotting K562 Cells Membrane Potentials Microscopy, Confocal Microscopy, Fluorescence Mitochondria / metabolism Molecular Sequence Data Plasmids / metabolism Precipitin Tests Promoter Regions, Genetic Protein Binding Proteins / metabolism* Proteins / physiology* Proto-Oncogene Proteins / metabolism Proto-Oncogene Proteins c-bcl-2* Time Factors Transcription Factors / metabolism* Transcription, Genetic Transfection Tumor Cells, Cultured Tumor Suppressor Protein p53 / metabolism Up-Regulation bcl-2-Associated X Protein |
| IF | 4.238 |
| 引用数 | 118 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | G-361(RCB0991) COLO 679(RCB0989) |