出版社：American Society for Biochemistry and Molecular Biology
摘要：Cholesteryl ester transfer protein (CETP) is a key factor in plasma reverse cholesterol transport and is implicated in the pathophysiology of atherogenic dyslipidemia. Variations observed in plasma CETP mass and activity in both normolipidemic and dyslipidemic individuals may reflect differences in CETP gene expression. We evaluated the respective roles of the Sp1 and Sp3 transcription factors on the promoter activity of the human CETP gene at a new Sp1/Sp3 site identified at position −690, and at two previously described Sp1/Sp3 sites at positions −37 and −629. In transient transfection in HepG2 cells, site-directed mutagenesis using luciferase reporter constructs containing a promoter fragment from +32 to −745 indicated that the new −690 site acts as a repressive element in reducing CETP promoter activity (−22%; P P P Taken together, our data demonstrate that Sp1 and Sp3 regulate human CETP promoter activity through three Sp1/Sp3 binding sites in a distinct manner, and that the Sp1/Sp3 ratio is a key factor in determining the relative contribution of these sites to total promoter activity.
