Inhibitory effect of the transcription factor encoded by the mutant mi microphthalmia allele on transactivation of mouse mast cell protease 7 gene.
The transcription factor encoded by the mi locus (MITF) is a transcription factor of the basic-helix-loop-helix zipper protein family. Mice of mi/mi genotype express a normal amount of abnormal MITF, whereas mice of tg/tg genotype do not express any MITFs due to the transgene insertional mutation. The effect of normal (+) and mutant (mi) MITFs on the expression of mouse mast cell protease (MMCP) 6 and 7 was examined. Both MMCP-6 and MMCP-7 are tryptases, and their coding regions with high homology are closely located on chromosome 17. Both MMCP-6 and MMCP-7 genes are expressed in normal cultured mast cells (+/+ CMCs). Although the transcription of MMCP-6 gene was severely suppressed in both mi/mi and tg/tg CMCs, that of MMCP-7 gene was severely suppressed only in mi/mi CMCs. The study identified the most significant segment for the transcription in the 5' flanking region of MMCP-7 gene. Unexpectedly, no CANNTG motifs were found that are recognized and bound by +-MITF in this segment. Instead, there was an AP-1 binding motif, and binding of c-Jun to the AP-1 motif significantly enhanced the transcription of MMCP-7 gene. The complex formation of c-Jun with either +-MITF or mi-MITF was demonstrated. The binding of +-MITF to c-Jun enhanced the transactivation of MMCP-7 gene, and that of mi-MITF suppressed the transactivation. Although the former complex was located only in the nucleus, the latter complex was predominantly found in the cytoplasm. The negative effect of mi-MITF on the transcription of MMCP-7 gene appeared to be executed through the interaction with c-Jun.
Ogihara
H
H
Department of Pathology, Osaka University Medical School, Suita, Japan.
Morii
E
E
Kim
D K
DK
Oboki
K
K
Kitamura
Y
Y
D021581:Active Transport, Cell Nucleus; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D046911:Macromolecular Substances; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D051739:Microphthalmia-Associated Transcription Factor; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D053802:Tryptases
D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; C509190:Tpsb2 protein, mouse; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D012697:Serine Endopeptidases; C509222:Tpsab1 protein, mouse; D053802:Tryptases