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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Transcriptional activation of human GM3 synthase (hST3Gal V) gene by valproic acid in ARPE-19 human retinal pigment epithelial cells

  • Song, Na-Ree (Department of Biotechnology and Brain Korea 21 Center for Silver-Bio Industrialization, Dong-A University) ;
  • Kim, Seok-Jo (Department of Biotechnology and Brain Korea 21 Center for Silver-Bio Industrialization, Dong-A University) ;
  • Kwon, Haw-Young (Department of Biotechnology and Brain Korea 21 Center for Silver-Bio Industrialization, Dong-A University) ;
  • Son, Sung-Wook (Department of Biotechnology and Brain Korea 21 Center for Silver-Bio Industrialization, Dong-A University) ;
  • Kim, Kyoung-Sook (Department of Biotechnology and Brain Korea 21 Center for Silver-Bio Industrialization, Dong-A University) ;
  • Ahn, Hee-Bae (Department of Ophthalmology, College of Medicine, Dong-A University) ;
  • Lee, Young-Choon (Department of Biotechnology and Brain Korea 21 Center for Silver-Bio Industrialization, Dong-A University)
  • Received : 2011.03.08
  • Accepted : 2011.04.15
  • Published : 2011.06.30
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Abstract

The present study demonstrated that valproic acid (VPA) transcriptionally regulates human GM3 synthase (hST3Gal V), which catalyzes ganglioside GM3 biosynthesis in ARPE-19 human retinal pigment epithelial cells. For this, we characterized the promoter region of the hST3Gal V gene. Functional analysis of the 5'-flanking region of the hST3Gal V gene revealed that the -177 to -83 region functions as the VPA-inducible promoter and that the CREB/ATF binding site at -143 is crucial for VPA-induced expression of hST3Gal V in ARPE-19 cells. In addition, the transcriptional activity of hST3Gal V induced by VPA in ARPE-19 cells was inhibited by SP600125, a c-Jun N-terminal kinase (JNK) inhibitor. In summary, our results identified the core promoter region in the hST3Gal V promoter and for the first time demonstrated that ATF2 binding to the CREB/ATF binding site at -143 is essential for transcriptional activation of hST3Gal V in VPA-induced ARPE-19 cells.

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References

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