Abstract
We investigated transactivation by NANOG in regulating growth and differentiation factor 3 (GDF3) expression in NCCIT cells. GDF3 expression was affected by shRNA-mediated downregulation and by exogenous overexpression of NANOG specifically, as well as by retinoic acid-mediated differentiation. GDF3 transcription was activated by NANOG, and the upstream region (-183 to -1) was sufficient to induce minimal transcriptional activity. Moreover, NANOG binds to the GDF3 minimal promoter in vivo and the transcriptional activity is mediated by NANOG transactivation domain. This study provides the first evidence that NANOG is a transcriptional activator of the expression of the oncogenic growth factor GDF3 in embryonic carcinoma cells.
Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Base Sequence
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Binding Sites / genetics
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Carcinoma, Embryonal / genetics*
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Carcinoma, Embryonal / metabolism*
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Carcinoma, Embryonal / pathology
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Cell Differentiation / drug effects
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Cell Line, Tumor
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Gene Expression Regulation, Neoplastic
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Growth Differentiation Factor 3 / genetics*
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HEK293 Cells
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Homeodomain Proteins / antagonists & inhibitors
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Homeodomain Proteins / chemistry
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Homeodomain Proteins / genetics*
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Homeodomain Proteins / metabolism*
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Humans
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Molecular Sequence Data
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Nanog Homeobox Protein
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Neoplastic Stem Cells / metabolism
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Neoplastic Stem Cells / pathology
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Pluripotent Stem Cells / metabolism
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Pluripotent Stem Cells / pathology
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Promoter Regions, Genetic
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Protein Structure, Tertiary
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RNA, Small Interfering / genetics
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Sequence Homology, Nucleic Acid
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Trans-Activators / antagonists & inhibitors
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Trans-Activators / chemistry
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Tretinoin / pharmacology
Substances
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GDF3 protein, human
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Growth Differentiation Factor 3
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Homeodomain Proteins
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NANOG protein, human
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Nanog Homeobox Protein
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RNA, Small Interfering
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Trans-Activators
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Tretinoin