In this study, we have shown that gene expression of human GD3 synthase (hST8Sia I) is suppressed by triptolide (TPL) in human melanoma SK-MEL-2 cells. To elucidate the mechanism underlying the down regulation of hST8Sia I gene expression in TPL-treated SK-MEL-2 cells, we characterized the TPL-inducible promoter region within the hST8Sia I gene using luciferase constructs carrying 5'-deletions of the hST8Sia I promoter. Functional analysis of the 5'-flanking region of the hST8Sia I gene demonstrated that the -1146 to -646 region, which contains putative binding sites for transcription factors c-Ets-1, CREB, AP-1 and NF-k{cyrillic}B, functions as the TPL-inducible promoter of hST8Sia I in SK-MEL-2 cells. Site-directed mutagenesis and ChIP analysis indicated that the NF-k{cyrillic}B binding site at -731 to -722 is crucial for TPL-induced suppression of hST8Sia I in SK-MEL-2 cells. This suggests that TPL induces down-regulation of hST8Sia I gene expression through NF-κB activation in human melanoma cells.
CITATION STYLE
Kwon, H. Y., Kim, S. J., Kim, C. H., Son, S. W., Kim, K. S., Lee, J. H., … Lee, Y. C. (2010). Triptolide downregulates human GD3 synthase (hST8Sia I) gene expression in SK-MEL-2 human melanoma cells. Experimental and Molecular Medicine, 42(12), 849–855. https://doi.org/10.3858/emm.2010.42.12.088
Mendeley helps you to discover research relevant for your work.