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http://dx.doi.org/10.5352/JLS.2010.20.9.1332

Transcriptional Regulation of Human GD3 Synthase (hST8Sia I) by Fenretinide in Human Neuroblastoma SH-SY-5Y Cells  

Kang, Nam-Young (Department of Biotechnology, College of Natural Resources and Life Science, Dong-A University)
Kwon, Haw-Young (Department of Biotechnology, College of Natural Resources and Life Science, Dong-A University)
Lee, Young-Choon (Department of Biotechnology, College of Natural Resources and Life Science, Dong-A University)
Publication Information
Journal of Life Science / v.20, no.9, 2010 , pp. 1332-1338 More about this Journal
Abstract
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.
Keywords
Human GD3 synthase; fenretinide; transcription factor; SH-SY5Y;
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1 Lovat, P. E., F. Di Sano, M. Corazzari, B. Fazi, R. Perrone Donnorso, A. D. J. Pearson, A. G. Hall, C. P. F. Redfern, and M. Piacentini. 2004. Gangliosides link the acidic sphingomyelinase- mediated induction of ceramide to 12- Lipoxygenase-dependent apoptosis of neuroblastoma in response to fenretinide. J. Natl. Cancer Inst. 96, 1288-1298.   DOI
2 Lovat, P. E., M. Corazzari, B. Goranov, M. Piacentini, and C. P. F. Redfern. 2004. Molecular mechanisms of fenretinide- induced apoptosis of neuroblastoma cells. Ann. N. Y. Acad. Sci. 1028, 81-89.   DOI   ScienceOn
3 Lovat, P. E., M. Corazzari, F. Di Sano, M. Piacentini, and C. P. F. Redfern. 2005. The role of gangliosides in fenretinide-induced apoptosis of neuroblastoma. Cancer Lett. 228, 105-110.   DOI
4 Malisan, F. and R. Testi. 2002. GD3 ganglioside and apoptosis. Biochim. Biophys. Acta, 1585, 179-187.   DOI   ScienceOn
5 Malisan, F. and R. Testi. 2002. GD3 in cellular ageing and apoptosis. Exp. Gerontol. 37, 1273-1282.   DOI
6 Svennerholm, L. 1980. Gangliosides and synaptic transmission. Adv. Exp. Med. Biol. 125, 533-544.   DOI
7 Baeuerle, P. A. and D. Baltimore. 1996. NF-${\kappa}B$: ten years after. Cell 87, 13-20.   DOI
8 Campbell Hewson, Q. D., P. E. Lovat, M. Corazzari, J. B. Catterall, and C. P. Redfern. 2005. The NF-${\kappa}B$ pathway mediates fenretinide-induced apoptosis in SH-SY5Y neuroblastoma cells. Apoptosis 10, 493-498.   DOI
9 Chen, F., V. Castranova, and X. Shi. 2001. New insights into the role of nuclear factor-${\kappa}B$ in cell growth regulation. Am. J. Pathol. 159, 387-397.   DOI   ScienceOn
10 Hail Jr, N., H. J. Kim, and R. Lotan. 2006. Mechanisns of fenretinide-induced apoptosis. Apoptosis 11, 1677-1694.   DOI
11 Hakomori, S. 1981.lycosphingolipids in cellular interaction, differentiation, and oncogenesis. Annu. Rev. Biochem. 50, 733-764.   DOI
12 Kwon, H. Y., H. M. Dae, N. R. Song, K. S. Kim, C. H. Kim, and Y. C. Lee. 2009. Valproic acid induces transcriptional activation of human GD3 synthase (hST8Sia I) in SK-N-BE(2)-C human neuroblastoma cells. Mol. Cells 27, 113-118.   DOI
13 Hakomori, S. and Y. Igarashi. 1993. Gangliosides and glycosphingolipids as modulators of cell growth, adhesion, and transmembrane signaling. Adv. Lipid Res. 25, 147-162.
14 Kang, N. Y., S. K Kang, Y. C. Lee, H. J. Choi, Y. S. Lee, S. Y. Cho, Y. S. Kim, J. H. Ko, and C. H. Kim. 2006. Transcriptional regulation of the human GD3 synthase gene expression in Fas-induced Jurkat T cells: a critical role of transcription factor NF-${\kappa}B$ in regulated expression. Glycobiology 16, 375-389.   DOI
15 Kang, N. Y., C. H. Kim, K. S. Kim, J. H. Ko, J. H. Lee, Y. K. Jeong, and Y. C. Lee. 2007. Expression of the human CMP-NeuAc:GM3 $\alpha$2,8 sialyltransferase (GD3 synthase) gene through the NF-${\kappa}B$ activation in human melanoma SK-MEL-2 cells. Biochim. Biophys. Acta 1769, 622-630.   DOI   ScienceOn