Transcriptional regulation of the human Sia-alpha2,3-Gal-beta1,4-GlcNAc-R:alpha2,8-sialyltransferase (hST8Sia III) by retinoic acid in human glioblastoma tumor cell line

Seok Jo Kim, Hee Jung Choi, Un Ho Jin, Young Choon Lee*, Cheorl Ho Kim

*Corresponding author for this work

Research output: Contribution to journalArticle

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Abstract

In this study, we have shown the transcriptional regulation of the human Sia-alpha2,3-Gal-beta1,4-GlcNAc-R:alpha2,8-sialyltransferase (hST8Sia III) induced by retinoic acid (RA), a potent neuronal cell regulator in glioblastoma cell line (U-87MG). The induction of hST8Sia III by RA is regulated at the transcriptional level in a dose- and time-dependent manner, as evidenced by reverse transcription-polymerase chain reaction (RT-PCR). To elucidate the mechanism underlying the regulation of hST8Sia III gene expression in RA-stimulated U-87MG cells, we characterized the promoter region of the hST8Sia III gene. Functional analysis of the 5′-flanking region of the hST8Sia III gene by the transient expression method showed that the - 1194 to - 816 region, which contains a retinoic acid nucleic receptor (RAR) at - 1000 to - 982, functions as the RA-inducible promoter in U-87MG cells. Site-directed mutagenesis indicated that the RA binding site at - 996 to - 991 is crucial for the RA-induced expression of the hST8Sia III in U-87MG cells. In addition, the transcriptional activity of hST8Sia III induced by RA in U-87MG cells was strongly inhibited by SP600125, c-Jun N-terminal Kinase (JNK) inhibitor, as determined by RT-PCR and luciferase assay of hST8Sia III promoter containing the - 1194 to - 816 regions. These results suggest that RA markedly modulates transcriptional regulation of hST8Sia III gene expression through JNK signal pathway in U-87MG cells.

Original languageEnglish (US)
Pages (from-to)451-457
Number of pages7
JournalBiochimica et Biophysica Acta - Gene Structure and Expression
Volume1759
Issue number10
DOIs
Publication statusPublished - Oct 1 2006

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Keywords

  • Gliobalstoma U-87MG cell
  • Human Sia-alpha2,3-Gal-beta1,4-GlcNAc-R:alpha2,8-sialyltransferase
  • JNK-dependent promoter activation
  • Retinoic acid nucleic receptor

ASJC Scopus subject areas

  • Structural Biology
  • Biophysics
  • Biochemistry
  • Genetics

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