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http://dx.doi.org/10.1007/s10059-009-0012-4

Valproic Acid Induces Transcriptional Activation of Human GD3 Synthase (hST8Sia I) in SK-N-BE(2)-C Human Neuroblastoma Cells  

Kwon, Haw-Young (Department of Biotechnology, Dong-A University)
Dae, Hyun-Mi (Department of Biotechnology, Dong-A University)
Song, Na-Ri (Department of Biotechnology, Dong-A University)
Kim, Kyoung-Sook (Brain Korea 21 Center for Silver-Bio Industrialization, Dong-A University)
Kim, Cheorl-Ho (Molecular and Cellular Glycobiology Unit, Department of Biological Sciences, SungKyunKwan University)
Lee, Young-Choon (Department of Biotechnology, Dong-A University)
Publication Information
Molecules and Cells / v.27, no.1, 2009 , pp. 113-118 More about this Journal
Abstract
In this study, we have shown the transcriptional regulation of the human GD3 synthase (hST8Sia I) induced by valproic acid (VPA) in human neuroblastoma SK-N-BE(2)-C cells. To elucidate the mechanism underlying the regulation of hST8Sia I gene expression in VPA-stimulated SK-N-BE(2)-C cells, we characterized the promoter region of the hST8Sia I gene. Functional analysis of the 5'-flanking region of the hST8Sia I gene by the transient expression method showed that the -1146 to -646 region, which contains putative binding sites for transcription factors c-Ets-1, CREB, AP-1 and NF-${\kappa}B$, functions as the VPA-inducible promoter of hST8Sia I in SK-N-BE(2)-C cells. Site-directed mutagenesis and electrophoretic mobility shift assay indicated that the NF-${\kappa}B$ binding site at -731 to -722 was crucial for the VPA-induced expression of hST8Sia I in SK-N-BE(2)-C cells. In addition, the transcriptional activity of hST8Sia I induced by VPA in SK-N-BE(2)-C cells was strongly inhibited by SP600125, which is a c-Jun N-terminal kinase (JNK) inhibitor, and $G{\ddot{O}}6976$, which is a protein kinase C (PKC) inhibitor, as determined by RT-PCR (reverse transcription-polymerase chain reaction) and luciferase assays. These results suggest that VPA markedly modulated transcriptional regulation of hST8Sia I gene expression through PKC/JNK signal pathways in SK-N-BE(2)-C cells.
Keywords
human GD3 synthase; SK-N-BE(2)-C; transcription factor; Valproic acid;
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