Mechanisms of sterol regulatory element-binding protein-2 (SREBP-2) regulation of human prostasin gene expression

    Authors

    M. Q. Chen; L. M. Chen;K. X. Chai

    Comments

    Authors: contact us about adding a copy of your work at STARS@ucf.edu

    Abbreviated Journal Title

    Biochem. Biophys. Res. Commun.

    Keywords

    electrophoretic mobility shift assay (EMSA); promoter activity assay; serine protease; glycosylphosphatidylinositol; DENSITY-LIPOPROTEIN RECEPTOR; EPITHELIAL SODIUM-CHANNEL; SERINE-PROTEASE; BREAST-CANCER; CELL-LINE; IDENTIFICATION; LOCALIZATION; ACTIVATORS; PROMOTER; GRADE; Biochemistry & Molecular Biology; Biophysics

    Abstract

    Prostasin is a glycosylphosphatidylinositol (GPT)-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. (c) 2006 Elsevier Inc. All rights reserved.

    Journal Title

    Biochemical and Biophysical Research Communications

    Volume

    346

    Issue/Number

    4

    Publication Date

    1-1-2006

    Document Type

    Article

    Language

    English

    First Page

    1245

    Last Page

    1253

    WOS Identifier

    WOS:000239016600018

    ISSN

    0006-291X

    Share

    COinS