Valproic acid enhances Oct4 promoter activity through PI3K/Akt/mTOR pathway activated nuclear receptors

Han Fang Teng, Pei Ning Li, Duen Ren Hou, Sin Wei Liu, Cheng Tao Lin, Moo Rung Loo, Chien Han Kao, Kwang Huei Lin, Shen Liang Chen

研究成果: 雜誌貢獻期刊論文同行評審

20 引文 斯高帕斯(Scopus)

摘要

Valproic acid (VPA) has been shown to increase the reprogramming efficiency of induced pluripotent stem cells (iPSC) from somatic cells, but the mechanism by which VPA enhances iPSC induction has not been defined. Here we demonstrated that VPA directly activated Oct4 promoter activity through activation of the PI3. K/Akt/mTOR signaling pathway that targeted the proximal hormone response element (HRE, -41. ~. -22) in this promoter. The activating effect of VPA is highly specific as similar compounds or constitutional isomers failed to instigate Oct4 promoter activity. We further demonstrated that the upstream 2 half-sites in this HRE were essential to the activating effect of VPA and they were targeted by a subset of nuclear receptors, such as COUP-TFII and TR2. These findings show the first time that NRs are implicated in the VPA stimulated expression of stem cell-specific factors and should invite more investigation on the cooperation between VPA and NRs on iPSC induction.

原文???core.languages.en_GB???
頁(從 - 到)147-158
頁數12
期刊Molecular and Cellular Endocrinology
383
發行號1-2
DOIs
出版狀態已出版 - 5 3月 2014

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