CREB involvement in TPA mediated sno regulation

• Main Authors: Hung-Lun Chiang, 江宏倫
• Other Authors: Wen-chang Lin
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/37916836831203691643

碩士 === 國立陽明大學 === 醫學生物技術研究所 === 94 === HL-60 is a human promyelocytic leukemia cell line. In previous studies, HL-60 cells are able to differentiate into macrophage / monocyte-like cells by phorbor ester (12-O-tetradecanoylphorbol 13-acetate [TPA]). In our study, when HL-60 treated with TPA, Sno mRNA is increased during the differentiation of HL-60 cells into the monocyte/macrophage lineage. The molecular mechanisms involved in transcriptional activation of Sno during differentiation of TPA-induced HL-60 cells are not well understood. It has been reported TPA induced the marked activation of protein kinase C (PKC)/ extracellular regulated kinases (ERKs) signal transduction pathway during the differentiation of HL-60 cells and subsequently led to the phosphorylation of cAMP-responsive element binding protein (CREB). CREB is a transcription activator and is capable of activating ST3 beta-galactoside alpha-2,3-sialyltransferase 5(GM3) gene expression upon TPA treatment. Thus, the up-regulated expression of sno might be the result of PKC/ERKs-dependent CREB activation in TPA stimulated HL-60 cells. Using prediction tools, sno promoter region contained putative cAMP-responsive element (CRE) sites. These functional CRE sites on the genome are maintained through evolution. In this study, we have used overexpression and knockdown approaches to examine the expression status of CREB on sno regulation. We found that the sno up regulation in AZ521 and 293T cells was mediated through CREB activation.