論文 - 詳細
| RRC ID | 45116 |
|---|---|
| 著者 | Harada G, Neng Q, Fujiki T, Katakura Y. |
| タイトル | Molecular mechanisms for the p38-induced cellular senescence in normal human fibroblast. |
| ジャーナル | J Biochem |
| Abstract |
We previously reported that TAK1, one of the mitogen-activated protein kinase kinase kinases (MAP3Ks), represses the transcription of the human telomerase reverse transcriptase (hTERT) gene in human cancer cells and induces cellular senescence in normal diploid human cells. On the basis of these results, we presumed a link between hTERT repression and the induction of cellular senescence. In this study, we identified the MAPK p38 as a downstream mediator of TAK1, which represses hTERT transcription. Further, we observed that hTERT expression was repressed in senescent normal human fibroblast, and was attenuated on treatment with SB203580, a p38-specific inhibitor, which suggests that p38 represses hTERT expression during cellular senescence. Next, we demonstrated that repression of hTERT, irrespective of the activation status of p38, is important for the induction of cellular senescence, by using hTERT-overexpressing cells and hTERT-knockdown cells. Our results suggested that p38 is activated during the serial passagings of normal human fibroblast, which results in the repression of hTERT transcription and induction of cellular senescence. |
| 巻・号 | 156(5) |
| ページ | 283-90 |
| 公開日 | 2014-11-1 |
| DOI | 10.1093/jb/mvu040 |
| PII | mvu040 |
| PMID | 24920674 |
| MeSH | Cells, Cultured Cellular Senescence* / genetics Fibroblasts / cytology* Fibroblasts / enzymology* Humans Telomerase / genetics Telomerase / metabolism Transcription, Genetic p38 Mitogen-Activated Protein Kinases / metabolism* |
| IF | 2.476 |
| 引用数 | 10 |
| 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
|
| 最多言及媒体 | |
| 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 | HUC-F2(RCB0436) A549 |