Chen Mengqian, Chen Li-Mei, Chai Karl X
Department of Molecular Biology and Microbiology, University of Central Florida, Orlando, FL 32816-2364, USA.
Biochem Biophys Res Commun. 2006 Aug 11;346(4):1245-53. doi: 10.1016/j.bbrc.2006.06.049. Epub 2006 Jun 16.
Prostasin is a glycosylphosphatidylinositol (GPI)-anchored serine protease and a suppressor of tumor cell invasion. We recently reported that the human prostasin gene is up-regulated by the transcription factor sterol regulatory element-binding protein-2 (SREBP-2). In the present study, we identified multiple SREBP-2 binding sites, known as sterol regulatory elements (SREs), located at positions -897, -538, +8, +71, and +98 (named SRE-897, SRE-538, SRE+8, SRE+71, and SRE+98) in the human prostasin gene promoter. Prostasin promoter-reporter constructs, representing serial deletions of the 5'-flanking region of the human prostasin gene, were transiently transfected into HEK-293 cells for evaluation of promoter activities. The region defined by nucleotides -17 to +232 of the prostasin gene promoter was shown to be essential for the basal transcriptional activity of the human prostasin gene. Mutagenesis of the five SREs was carried out for evaluation of their roles in SREBP-2 up-regulation. SRE+98, a novel functional sterol regulatory element, was found to be the major site for the stimulatory response of prostasin gene expression to SREBP-2.
前列腺素酶是一种糖基磷脂酰肌醇（GPI）锚定的丝氨酸蛋白酶，也是肿瘤细胞侵袭的抑制因子。我们最近报道，人类前列腺素酶基因受转录因子固醇调节元件结合蛋白-2（SREBP-2）上调。在本研究中，我们在人类前列腺素酶基因启动子中鉴定出多个SREBP-2结合位点，即固醇调节元件（SREs），位于-897、-538、+8、+71和+98位置（分别命名为SRE-897、SRE-538、SRE+8、SRE+71和SRE+98）。将代表人类前列腺素酶基因5'侧翼区域系列缺失的前列腺素酶启动子-报告基因构建体瞬时转染至HEK-293细胞中，以评估启动子活性。结果表明，前列腺素酶基因启动子核苷酸-17至+232所定义的区域对人类前列腺素酶基因的基础转录活性至关重要。对五个SREs进行诱变，以评估它们在SREBP-2上调中的作用。发现SRE+98是一种新型功能性固醇调节元件，是前列腺素酶基因表达对SREBP-2刺激反应的主要位点。
