論文 - 詳細
| RRC ID | 45163 |
|---|---|
| 著者 | Yamashita S, Ogawa K, Ikei T, Fujiki T, Katakura Y. |
| タイトル | FOXO3a potentiates hTERT gene expression by activating c-MYC and extends the replicative life-span of human fibroblast. |
| ジャーナル | PLoS One |
| Abstract |
In our previous studies, we reported that SIRT1 prevents cellular senescence in human fibroblast, and that SIRT1-induced inhibition of cellular senescence is due to enhanced hTERT gene expression. In this study, we investigate the molecular mechanisms behind SIRT1-induced potentiation of hTERT transcription and show that FOXO3a functions downstream of SIRT1 and prevents the induction of cellular senescence by enhancing hTERT gene expression. Furthermore, we found that FOXO3a-induced potentiation of hTERT gene expression is regulated in a c-MYC/E-box dependent manner. In addition, we found that FOXO3a binds to the novel binding element in the c-MYC promoter, and this interaction activates the transcription of the c-MYC gene. The resulting increase in c-MYC leads to higher levels of c-MYC recruited to the hTERT promoter and, in turn, activates hTERT gene expression. Taken together, this pathway might constitute the molecular basis for the anti-senescence effects of SIRT1 and FOXO3a. |
| 巻・号 | 9(7) |
| ページ | e101864 |
| 公開日 | 2014-1-1 |
| DOI | 10.1371/journal.pone.0101864 |
| PII | PONE-D-14-10840 |
| PMID | 25000517 |
| PMC | PMC4085005 |
| MeSH | Base Sequence Cell Line Cellular Senescence* Fibroblasts / cytology* Forkhead Box Protein O3 Forkhead Transcription Factors / metabolism* Gene Expression Regulation, Enzymologic* Humans Promoter Regions, Genetic / genetics Proto-Oncogene Proteins c-myc / genetics Proto-Oncogene Proteins c-myc / metabolism* Sirtuin 1 / metabolism Telomerase / genetics* Transcription, Genetic |
| IF | 2.74 |
| 引用数 | 18 |
| WOS 分野 | MULTIDISCIPLINARY SCIENCES |
| 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 | 3 |
| 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) |