Transcriptional activation of human GM3 synthase (hST3Gal V) gene by valproic acid in ARPE-19 human retinal pigment epithelial cells

• Published in: BMB reports Vol. 44; no. 6; pp. 405 - 409
• Main Authors: Song, N.R., Dong-A University, Busan, Republic of Korea, Kim, S.J., Dong-A University, Busan, Republic of Korea, Kwon, H.Y., Dong-A University, Busan, Republic of Korea, Son, S.W., Dong-A University, Busan, Republic of Korea, Kim, K.S., Dong-A University, Busan, Republic of Korea, Ahn, H.B., Dong-A University, Busan, Republic of Korea, Lee, Y.C., Dong-A University, Busan, Republic of Korea
• Format: Journal Article
• Language: English
• Published: Korea (South) 생화학분자생물학회 01.06.2011
• Subjects: Activating Transcription Factor 2 - genetics; Activating Transcription Factor 2 - metabolism; Animals; ARPE-19; Binding Sites; Cell Line; Enzyme Inhibitors - pharmacology; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - physiology; Gene Expression Regulation, Enzymologic - drug effects; Human GM3 synthase; Humans; JNK Mitogen-Activated Protein Kinases - genetics; JNK Mitogen-Activated Protein Kinases - metabolism; Promoter Regions, Genetic; Retinal Pigment Epithelium - cytology; SFINGOLIPIDOS; Sialyltransferases - genetics; Sialyltransferases - metabolism; Signal Transduction - physiology; SPHINGOLIPIDE; SPHINGOLIPIDS; Transcriptional Activation - drug effects; transcriptional regulation; Valproic acid; Valproic Acid - pharmacology; 화학
• ISSN: 1976-6696; 1976-670X
• DOI: 10.5483/bmbrep.2011.44.6.405

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.