RRC ID |
41564
|
Author |
Naraba H, Yokoyama C, Tago N, Murakami M, Kudo I, Fueki M, Oh-Ishi S, Tanabe T.
|
Title |
Transcriptional regulation of the membrane-associated prostaglandin E2 synthase gene. Essential role of the transcription factor Egr-1.
|
Journal |
J Biol Chem
|
Abstract |
Membrane-associated prostaglandin (PG) E2 synthase (mPGES) is an inducible terminal enzyme in the biosynthetic pathway for prostaglandin E2, 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.
|
Volume |
277(32)
|
Pages |
28601-8
|
Published |
2002-8-9
|
DOI |
10.1074/jbc.M203618200
|
PII |
S0021-9258(20)70256-5
|
PMID |
12034740
|
MeSH |
Amino Acid Motifs
Animals
Base Sequence
Blotting, Northern
Blotting, Western
Cell Line
Cloning, Molecular
DNA-Binding Proteins / metabolism
DNA-Binding Proteins / physiology*
Early Growth Response Protein 1
Exons
Gene Deletion
Genes, Reporter
Immediate-Early Proteins*
Mice
Mice, Transgenic
Models, Genetic
Molecular Sequence Data
Mutagenesis, Site-Directed
Mutation
Plasmids / metabolism
Promoter Regions, Genetic
Prostaglandin-Endoperoxide Synthases / biosynthesis
Prostaglandin-Endoperoxide Synthases / genetics*
Protein Binding
Tissue Distribution
Transcription Factors / metabolism
Transcription Factors / physiology*
Transcription, Genetic*
|
IF |
4.238
|
Times Cited |
121
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
Resource |
Human and Animal Cells |
MC3T3-E1(RCB1126)
RAW 264(RCB0535) |