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

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:383

Article

Teng, Han Fang¹  Li, Pei Ning¹  Hou, Duen Ren²  Liu, Sin Wei²  Lin, Cheng Tao¹  Loo, Moo Rung¹  Kao, Chien Han¹  Lin, Kwang Huei³  Chen, Shen Liang¹ 

[1] Natl Cent Univ, Dept Life Sci, Jhongli 32001, Taiwan

[2] Natl Cent Univ, Dept Chem, Jhongli 32001, Taiwan

[3] Chang Gung Univ, Dept Biochem, Tao Yuan 333, Taiwan

关键词: Muscle;    Oct4;    Nuclear receptor;    iPSC;    VPA;    Akt;   

DOI  :  10.1016/j.mce.2013.12.008

来源: Elsevier

【 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 iPSG 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. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

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