Mechanisms of sterol regulatory element-binding protein-2 (SREBP-2) regulation of human prostasin gene expression.
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.
Chen
Mengqian
M
Department of Molecular Biology and Microbiology, University of Central Florida, Orlando, FL 32816-2364, USA.
Chen
Li-Mei
LM
Chai
Karl X
KX
D024506:5' Flanking Region / Q000502:physiology; D001665:Binding Sites; D002478:Cells, Cultured; D015870:Gene Expression / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000502:physiology*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D027602:Serum Response Element / Q000502:physiology; D051782:Sterol Regulatory Element Binding Protein 2 / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology; D000099271:Prostasin
D012697:Serine Endopeptidases; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors; D000099271:Prostasin