Interaction and cooperation of mi transcription factor (MITF) and myc-associated zinc-finger protein-related factor (MAZR) for transcription of mouse mast cell protease 6 gene.
The mi transcription factor (MITF) is a basic-helix-loop-helix leucine zipper (bHLH-Zip) transcription factor that is important for the normal phenotypic expression of mast cells. Most transcription factors function in cooperation with other factors by protein-protein interactions. To search proteins interacting with MITF, we carried out a yeast two-hybrid screen and isolated Myc-associated zinc-finger protein related factor (MAZR) as a partner of MITF. When expressed with MITF in NIH/3T3 cells, MAZR was colocalized with MITF. The association of MAZR with MITF was further confirmed by a co-immunoprecipitation study and in vitro binding assay. The zinc-finger domain of MAZR and the Zip domain of MITF were essential for the interaction. MAZR was expressed in cultured mast cells and MST mastocytoma cells containing mouse mast cell protease (mMCP)-6 transcript abundantly. The overexpression of dominant negative MAZR in MST mastocytoma cells reduced the amount of mMCP-6 mRNA. The simultaneous transfection of MAZR and MITF significantly increased the promoter activity of the mMCP-6 gene, indicating that the MAZR and MITF synergistically transactivated the mMCP-6 gene. MAZR appeared to play important roles in the normal phenotypic expression of mast cells in association with MITF.
Morii
Eiichi
E
Department of Pathology (Room C2), Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan. morii@patho.med.osaka-u.ac.jp
Oboki
Keisuke
K
Kataoka
Tatsuki R
TR
Igarashi
Kazuhiko
K
Kitamura
Yukihiko
Y
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005799:Genes, Dominant; D049452:Green Fluorescent Proteins; D006801:Humans; D007150:Immunohistochemistry; D019169:Jurkat Cells; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D053802:Tryptases; D014407:Tumor Cells, Cultured; D020798:Two-Hybrid System Techniques; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D008164:Luminescent Proteins; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D012333:RNA, Messenger; C509190:Tpsb2 protein, mouse; D014157:Transcription Factors; C076035:c-MYC-associated zinc finger protein; D049452:Green Fluorescent Proteins; D012697:Serine Endopeptidases; C509222:Tpsab1 protein, mouse; D053802:Tryptases