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Papers In Press, published online ahead of print May 28, 2002
Pharmacology, National Cardiovascular Center Research Institute, Suita, Osaka 565-8565
Corresponding Author: naraba{at}ri.ncvc.go.jp
Membrane-associated prostaglandin (PG) E2 synthase (mPGES) is an inducible terminal enzyme in the biosynthetic pathway for PGE2, which participates in many biological processes. In this study, we investigated the molecular mechanism controlling the inducible expression of mPGES. The mouse mPGES gene consisted of three exons, and its 5'-proximal promoter contained consensus motifs for the binding of several transcription factors. Transgenic expression in mice of the mouse mPGES promoter flanked by a reporter gene resulted in stimulus-dependent induction of the reporter in tissues where mPGES was intrinsically induced. Deletion and site-specific mutation analyses of the 5'-flanking region demonstrated that stimulus-inducible expression of mouse and human mPGES required tandem GC boxes adjacent to the initiation site. The stimulus-induced GC box-binding activity was present in nuclear extracts of cells, in which the proximal GC box was essential for binding. An 80-kDa stimulus-inducible nuclear protein that bound to this GC box was identified as the transcription factor Egr-1 (for early growth response-1). These results suggest that Egr-1 is a key transcription factor in regulating the inducible expression of mPGES.
J. Biol. Chem, 10.1074/jbc.M203618200
Submitted on April 15, 2002
Revised on May 23, 2002
Accepted on May 23, 2002
Transcriptional regulation of the membrane-associated prostaglandin E2 synthase gene. Esential role of the transcription factor EGR-1
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