論文 - 詳細
| RRC ID | 54079 |
|---|---|
| 著者 | Park AM, Tsunoda I, Yoshie O. |
| タイトル | Heat shock protein 27 promotes cell cycle progression by down-regulating E2F transcription factor 4 and retinoblastoma family protein p130. |
| ジャーナル | J Biol Chem |
| Abstract |
Heat shock protein 27 (HSP27) protects cells under stress. Here, we demonstrate that HSP27 also promotes cell cycle progression of MRC-5 human lung fibroblast cells. Serum starvation for 24 h induced G1 arrest in these cells, and upon serum refeeding, the cells initiated cell cycle progression accompanied by an increase in HSP27 protein levels. HSP27 levels peaked at 12 h, and transcriptional up-regulation of six G2/M-related genes (CCNA2, CCNB1, CCNB2, CDC25C, CDCA3, and CDK1) peaked at 24-48 h. siRNA-mediated HSP27 silencing in proliferating MRC-5 cells induced G2 arrest coinciding with down-regulation of these six genes. Of note, the promoters of all of these genes have the cell cycle-dependent element and/or the cell cycle gene-homology region. These promoter regions are known to be bound by the E2F family proteins (E2F-1 to E2F-8) and retinoblastoma (RB) family proteins (RB1, p107, and p130), among which E2F-4 and p130 were strongly up-regulated in HSP27-knockdown cells. E2F-4 or p130 knockdown concomitant with the HSP27 knockdown rescued MRC-5 cells from G2 arrest and up-regulated the six cell cycle genes. Moreover, we observed cellular senescence in MRC-5 cells on day 3 after the HSP27 knockdown, as evidenced by increased senescence-associated β-gal activity and up-regulated inflammatory cytokines. The cellular senescence was also suppressed by the concomitant knockdown of E2F-4/HSP27 or p130/HSP27. Our findings indicate that HSP27 promotes cell cycle progression of MRC-5 cells by suppressing expression of the transcriptional repressors E2F-4 and p130. |
| 巻・号 | 293(41) |
| ページ | 15815-15826 |
| 公開日 | 2018-10-12 |
| DOI | 10.1074/jbc.RA118.003310 |
| PII | S0021-9258(20)35124-3 |
| PMID | 30166342 |
| PMC | PMC6187643 |
| MeSH | Cell Cycle* Cell Line, Tumor Cell Proliferation Cellular Senescence Down-Regulation E2F4 Transcription Factor / metabolism* Fibroblasts / metabolism G2 Phase Gene Silencing HSP27 Heat-Shock Proteins / metabolism* Heat-Shock Proteins Humans Lung / metabolism Molecular Chaperones Oxygen / chemistry RNA, Small Interfering / metabolism Retinoblastoma-Like Protein p130 / metabolism* Tumor Suppressor Protein p53 / metabolism Up-Regulation |
| IF | 4.238 |
| 引用数 | 4 |
| 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 | X(Twitter) |
| 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 | MRC-5(RCB0211) |