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KMID : 0578320090270010113
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Molecules and Cells
2009 Volume.27 No. 1 p.113 ~ p.118
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Valproic Acid Induces Transcriptional Activation of Human GD3 Synthase (hST8Sia I) in SK-N-BE(2)-C Human Neuroblastoma Cells
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Kwon Haw-Young
Dae Hyun-Mi
Song Na-Ri
Kim Kyoung-Sook
Kim Cheorl-ho
Lee Young-Choon
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Abstract
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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-?첕, 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-?첕 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 G횜6976, 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.
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KEYWORD
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human GD3 synthase, SK-N-BE(2)-C, transcription factor, Valproic acid
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