Molecular mechanisms for the p38-induced cellular senescence in normal human fibroblast

Gakuro Harada, Qian Neng, Tsukasa Fujiki, Yoshinori Katakura

研究成果: ジャーナルへの寄稿学術誌査読

15 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)283-290
ページ数8
ジャーナルJournal of biochemistry
156
5
DOI
出版ステータス出版済み - 2014

!!!All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子生物学

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