title: Transcriptional activation of human GM3 synthase (hST3Gal V) gene by valproic acid in ARPE-19 human retinal pigment epithelial cells.
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.
authors.affiliation: Department of Biotechnology and Brain Korea 21 Center for Silver-Bio Industrialization, Dong-A University, Busan 604-714, Korea.
authors.forename: Naree
authors.initials: N
authors.lastname: Song
authors.forename: Seok-Jo
authors.initials: SJ
authors.lastname: Kim
authors.forename: Haw-Young
authors.initials: HY
authors.lastname: Kwon
authors.forename: Sung-Wook
authors.initials: SW
authors.lastname: Son
authors.forename: Kyoung-Sook
authors.initials: KS
authors.lastname: Kim
authors.forename: Hee-Bae
authors.initials: HB
authors.lastname: Ahn
authors.forename: Young-Choon
authors.initials: YC
authors.lastname: Lee
mesh_terms: D051698:Activating Transcription Factor 2 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D055213:Retinal Pigment Epithelium / Q000166:cytology*; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects*; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D004791:Enzyme Inhibitors; D014635:Valproic Acid; D012799:Sialyltransferases; C021343:haematoside synthetase; D048031:JNK Mitogen-Activated Protein Kinases