title: Synergy of PEBP2/CBF with mi transcription factor (MITF) for transactivation of mouse mast cell protease 6 gene.
abstract: The mi locus encodes a member of the basic - helix - loop - helix - leucine zipper (bHLH-Zip) protein family of transcription factors (hereafter called MITF). Although the bHLH-Zip family transcription factors generally recognize and bind CANNTG motifs, the expression of mouse mast cell protease 6 (MMCP-6) gene is regulated by MITF through the GACCTG motif in the promoter region. The GACCTG motif was partly overlapped the TGTGGTC sequence, which was bound by polyomavirus enhancer binding protein 2 (PEBP2). In the present study, the effect of PEBP2 on the expression of MMCP-6 gene was examined. PEBP2 that is composed of alpha and beta subunits was expressed by mast cell lines and cultured mast cells derived from spleen. The overexpression of dominant negative PEBP2 cDNA reduced the expression of MMCP-6. Moreover, the simultaneous transfection of the plasmid containing MITF cDNA and the plasmid containing PEBP2 cDNA increased the MMCP-6 promoter activity. For the synergistic action of PEBP2 and MITF, the intact GACCTG and TGTGGTC motifs were prerequisite. The PEBP2alphaB1 mutant which lacked the region downstream from the Runt domain did not bind MITF and lost the synergistic function. These results indicated that PEBP2 and MITF synergistically transactivated the MMCP-6 gene and that the region downstream from the Runt domain of PEBP2alphaB1 was essential for the physical and functional interactions with MITF.
authors.affiliation: Department of Pathology, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ogihara
authors.forename: T
authors.initials: T
authors.lastname: Kanno
authors.forename: E
authors.initials: E
authors.lastname: Morii
authors.forename: D K
authors.initials: DK
authors.lastname: Kim
authors.forename: Y M
authors.initials: YM
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.forename: W Y
authors.initials: WY
authors.lastname: Kim
authors.forename: S
authors.initials: S
authors.lastname: Nomura
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
authors.forename: Y
authors.initials: Y
authors.lastname: Kitamura
mesh_terms: D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004357:Drug Synergism; D005260:Female; D005786:Gene Expression Regulation; D018257:Helix-Loop-Helix Motifs; D016350:Leucine Zippers; D008297:Male; D008407:Mast Cells / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D051739:Microphthalmia-Associated Transcription Factor; D016296:Mutagenesis; D012697:Serine Endopeptidases / Q000235:genetics*; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D053802:Tryptases
chemical_list: D004268:DNA-Binding Proteins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; C509190:Tpsb2 protein, mouse; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D012697:Serine Endopeptidases; C509222:Tpsab1 protein, mouse; D053802:Tryptases