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

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题名:	Valproic acid enhances Oct4 promoter activity through PI3K/Akt/mTOR pathway activated nuclear receptors
作者:	陳盛良;Teng, Han Fang;Li, Pei Ning;Hou, Duen Ren;Liu, Sin Wei;Lin, Cheng Tao;Loo, Moo Rung;Kao, Chien Han;Lin, Kwang Huei;Chen, Shen Liang
贡献者:	生醫理工學院生命科學系
关键词:	Activated;Akt;Animals;Base Sequence;Cell Differentiation;Cell Line, Tumor;Cellular Reprogramming;Cooperation;COUP Transcription Factor II - genetics;COUP Transcription Factor II - metabolism;Gene Expression Regulation;Hormones;induced pluripotent stem cells;Induced Pluripotent Stem Cells - cytology;Induced Pluripotent Stem Cells - drug effects;Induced Pluripotent Stem Cells - metabolism;iPSC;Isomers;Mice;Molecular Sequence Data;Muscle;Muscle Cells - cytology;Muscle Cells - drug effects;Muscle Cells - metabolism;Nuclear receptor;Nuclear Receptor Subfamily 2, Group C, Member 1 - genetics;Nuclear Receptor Subfamily 2, Group C, Member 1 - metabolism;Oct4;Octamer Transcription Factor-3 - agonists;Octamer Transcription Factor-3 - genetics;Octamer Transcription Factor-3 - metabolism;Pathways;Phosphatidylinositol 3-Kinases - genetics;Phosphatidylinositol 3-Kinases - metabolism;Promoter Regions, Genetic;Protein Binding;Proto-Oncogene Proteins c-akt - genetics;Proto-Oncogene Proteins c-akt - metabolism;Receptors;Signal Transduction;somatic cells;Stem cells;TOR Serine-Threonine Kinases - genetics;TOR Serine-Threonine Kinases - metabolism;Upstream;valproic acid;Valproic Acid - analogs & derivatives;Valproic Acid - pharmacology;VPA
日期:	2014-03-05
上传时间:	2026-04-23 11:14:18 (UTC+8)
出版者:	Elsevier Ireland Ltd;Ireland: Elsevier Ireland Ltd
摘要:	摘要： •VPA activates Oct4 promoter through a hormone response element (HRE, −41~−22).•The upstream 2 half-sites in this HRE are essential to the activating effect of VPA.•These upstream 2 half-sites are targeted by a subset of nuclear receptors.•The signal of VPA is transduced through activation of the PI3K/Akt/mTOR pathway. 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 PI3K/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. 其他題名： Mol Cell Endocrinol 出版者： Ireland: Elsevier Ireland Ltd 出版日期： 2014-03-05 出處： Molecular and cellular endocrinology, 2014-03, Vol.383 (1-2), p.147-158 版權： 2013 Elsevier Ireland Ltd 版權： Copyright © 2013 Elsevier Ireland Ltd. All rights reserved. 識別號： ISSN: 0303-7207 識別號： ISSN: 1872-8057 識別號： EISSN: 1872-8057 識別號： DOI: 10.1016/j.mce.2013.12.008 識別號： PMID: 24361750
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