Abstract:
: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.
journal_name
Mol Cell Endocrinoljournal_title
Molecular and cellular endocrinologyauthors
Teng HF,Li PN,Hou DR,Liu SW,Lin CT,Loo MR,Kao CH,Lin KH,Chen SLdoi
10.1016/j.mce.2013.12.008subject
Has Abstractpub_date
2014-03-05 00:00:00pages
147-58issue
1-2eissn
0303-7207issn
1872-8057pii
S0303-7207(13)00523-6journal_volume
383pub_type
杂志文章abstract::Aggresome formation, a cellular response to misfolded protein aggregates, is linked to cancer and neurodegenerative disorders. Previously we showed that Gag-v-ErbA (v-ErbA), a retroviral variant of the thyroid hormone receptor (TRα1), accumulates in and sequesters TRα1 into cytoplasmic foci. Here, we show that foci re...
journal_title:Molecular and cellular endocrinology
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journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
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journal_title:Molecular and cellular endocrinology
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pub_type: 杂志文章
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