RRC ID 41564
著者 Naraba H, Yokoyama C, Tago N, Murakami M, Kudo I, Fueki M, Oh-Ishi S, Tanabe T.
タイトル Transcriptional regulation of the membrane-associated prostaglandin E2 synthase gene. Essential role of the transcription factor Egr-1.
ジャーナル 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.
巻・号 277(32)
ページ 28601-8
公開日 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
引用数 121
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 MC3T3-E1(RCB1126) RAW 264(RCB0535)