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
リソース情報
ヒト・動物細胞 HUC-F2(RCB0436)