| 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
|
| リソース情報 |
| ヒト・動物細胞 |
G-361(RCB0991)
COLO 679(RCB0989) |
