Title

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

Authors

Authors

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

Comments

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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

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