Cordycepin-mediated transcriptional regulation of human GD3 synthase (hST8Sia I) in human neuroblastoma SK-N-BE(2)-C cells.
In the present study, we firstly found that cordycepin elevated the gene expression of the human GD3 synthase (hST8Sia I) in human neuroblastoma SK-N-BE(2)-C cells. To elucidate the mechanism underlying the upregulation of hST8Sia I gene expression in cordycepin-treated SK-N-BE(2)-C cells, functional characterization of the promoter region of the hST8Sia I gene was performed. Analysis of promoter activity using varying lengths of 5'-flanking region showed a dramatic increase by cordycepin in the -1146 to -646 region, which contains putative binding sites for transcription factors c-Ets-1, CREB, AP-1, and NF-κB. Site-directed mutagenesis for these binding sites and chromatin immunoprecipitation assay revealed that the NF-κB binding site at -731 to -722 is essential for the cordycepin-induced expression of the hST8Sia I in SK-N-BE(2)-C cells. Moreover, the hST8Sia I expression induced by cordycepin was significantly repressed by pyrrolidinedithiocarbamate, an inhibitor of NF-κB. These results suggested that cordycepin induces upregulation of hST8Sia I gene expression through NF-κB activation in SK-N-BE(2)-C cells.
College of Natural Resources and Life Science, Dong-A University, Busan 604-714, South Korea.
Ji-Sue
JS
Baik
Kyoung-Sook
KS
Kim
Hyung-In
HI
Moon
Hyun-Kyu
HK
An
Shin-Ji
SJ
Park
Cheorl-Ho
CH
Kim
Young-Choon
YC
Lee
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003839:Deoxyadenosines / Q000494:pharmacology*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009447:Neuroblastoma / Q000201:enzymology; D011401:Promoter Regions, Genetic; D012799:Sialyltransferases / Q000096:biosynthesis*; D015533:Transcriptional Activation; D015854:Up-Regulation
D003839:Deoxyadenosines; D016328:NF-kappa B; D012799:Sialyltransferases; C043662:alpha-N-acetylneuraminate alpha-2,8-sialyltransferase; C058120:cordycepin
SK-N-BE(2)-C cell; cordycepin; human GD3 synthase; transcription factor