• Title/Summary/Keyword: fenretinide

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Transcriptional Regulation of Human GD3 Synthase (hST8Sia I) by Fenretinide in Human Neuroblastoma SH-SY-5Y Cells (사람 신경모세포종 세포주 SH-SY5Y에서 fenretinide에 의한 GD3합성효소(hST8Sia I)의 전사조절기작)

  • Kang, Nam-Young;Kwon, Haw-Young;Lee, Young-Choon
    • Journal of Life Science
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    • v.20 no.9
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    • pp.1332-1338
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    • 2010
  • To elucidate the mechanism underlying the regulation of hST8Sia I gene expression in FenR-induced SH-SY5Y cells, we characterized the promoter region of the hST8Sia I gene. Functional analysis of the 5'-flanking region of the hST8Sia I gene showed that the -1146 to -646 region functions as the FenR-inducible promoter of hST8Sia I in SH-SY5Y cells. Site-directed mutagenesis indicated that the NF-&B binding site at -731 to -722 was crucial for the FenR-induced expression of hST8Sia I in SH-SY5Y cells. To investigate which signal transduction pathway was involved in FenR-stimulated induction of hST8Sia I in SH-SY5Y cells, we performed Western blot analysis using phospho-specific antibodies in order to measure their degree of regulatory phosphorylation. Phosphorylations of AKT and RelA (p65) subunit of NF-${\kappa}B$ were significantly elevated in cytosolic and nuclear fractions of FenR-stimulated SH-SY5Y cells, respectively, than in control or DMSO-treated SH-SY5Y cells. These results suggest that FenR induce transcriptional up-regulation of hST8Sia I gene expression through translocation of RelA (p65) subunit of NF-${\kappa}B$ to nucleus by AKT signal pathway in SH-SY5Y cells.