New classification of infantile leukemia using lineage-specific transcription

使用谱系特异性转录对婴儿白血病进行新分类

• 批准号: 06670759
• 负责人: ITO Etsuro
• 金额: $ 1.34万
• 依托单位: HIROSAKI UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670759/
• 关键词: MEGAKARYOCYTES; NF-E2 TRANSCRIPTION FACTOR; MAF FAMILY; 組織特異的転写因子

Transcription factor NF-E2, which is heterodimeric protein complex comprised of products of p45 and the small maf family protooncogene (p18), is crucial for regulation of erythroid-specific gene expression and platelet formation. To characterize human p18, we isolated human cDNAs encoding the small Maf family protein MafK and MafG.The mafK gene and mafG gene encode proteins consisting of 156 and 162 amino acid residues, respectively and the molecular weight of these proteins are approximately 18kDa. MafK and MafG contain a basic DNA binding domain and a leucin zipper and lack putative trans-activator domain. The deduced amino acie sequence of human MafK or MafG showed 93% identity with that of its putative counterpart in chicken. The bacterially expressed MafK and MafG proteins form heterodimers with p45, which can efficiently bind to the NF-E2 probe. The homodimers of small Maf proteins also bind to NF-E2 probe.However, binding of p45/small Maf heterodimer to NF-E2 probe is more prominent than that of small Maf homodimers. In transient transfection assays, small Mafs activate transcription of NF-E2 site dependent reporter genes in the presence of p45, whereas small Mafs repress the transcription in the abscence of p45. mRNAs for MafK and MafG are detected in all human tissues examined to date. The level of mafK transcripts were relatively high in heart, skeletal muscle and placenta. The level of mafG transcripts were less variable among tissues. The mafK and mafG mRNAs are expressed in all hematopoietic cell lines including erythroid and megakaryocytic lineages and the blast cells from all cases with infantile leukemia. These results suggest that human small Mafs play important regulatory roles in hematopoietic cells as a partner of p45 NF-E2 or the other CNC family proteins.

转录因子NF-E2是由p45和小maf家族原癌基因（p18）的产物组成的异二聚体蛋白复合物，其对于调节红系特异性基因表达和血小板形成至关重要。为了研究人p18的特性，我们分离了人Maf家族小分子蛋白MafK和MafG的cDNA，MafK基因和MafG基因分别编码由156和162个氨基酸残基组成的蛋白质，这些蛋白质的分子量约为18 kDa。MafK和MafG含有一个基本的DNA结合结构域和一个亮氨酸拉链，缺乏假定的反式激活子结构域。推导的人MafK和MafG的氨基酸序列与鸡MafK和MafG的氨基酸序列有93%的同源性。细菌表达的MafK和MafG蛋白与p45形成异源二聚体，其可以有效地结合NF-E2探针。小分子Maf蛋白的同源二聚体也能与NF-E2探针结合，但p45/小分子Maf异源二聚体与NF-E2探针的结合比小分子Maf同源二聚体更显著。在瞬时转染试验中，小Maf在p45存在下激活NF-E2位点依赖性报告基因的转录，而小Maf在p45存在下抑制转录。MafK和MafG的mRNA在迄今为止检查的所有人类组织中检测到。mafK在心脏、骨骼肌和胎盘中的表达水平较高。组织间mafG转录水平变化较小。mafK和mafG mRNA在所有造血细胞系中表达，包括红系和巨核细胞谱系以及来自所有婴儿白血病病例的母细胞。这些结果表明，人小Mafs作为p45 NF-E2或其他CNC家族蛋白的伴侣在造血细胞中发挥重要的调节作用。

项目成果

Ito, E., 1.Ito, E., Kasai, M., Hayashi, Y., Toki, T., Arai, K., Yokoyama, S., Kato, K., Tachibna, N., Yamamoto, M.and Yokoyama, M.: "Expression of erythroid-specific genes in acute megakaryoblastic leukaemia and transient myeloproliferative disorder in Do

伊藤 E.、1.伊藤 E.、葛西 M.、林 Y.、土木 T.、荒井 K.、横山 S.、加藤 K.、立名 N.、山本 M

Toki, T., Itoh, J., Arai, K., Kitazawa, J., Yokoyama, M., Igarashi, K., Yamamoto, M.and Ito, E.: "Abundant expression of erythroid transcription factor p45 NF-E2 mRNA in human peripheral granulocytes" Biochem.Biophys.Res.Commun.(in press).

Toki, T.、Itoh, J.、Arai, K.、Kitazawa, J.、Yokoyama, M.、Igarashi, K.、Yamamoto, M. 和 Ito, E.：“红系转录因子 p45 NF- 的丰富表达

Ito, E.: "Expression of erythroid-spccific genes in acute megakaryoblastic leukaemia and transient myeloproliferative disorder in Down's syndrome" Brit. J. Haematol.,. 90. 607-614 (1995)

Ito, E.：“急性巨核细胞白血病和唐氏综合症短暂性骨髓增殖性疾病中红细胞特异性基因的表达”，英国。

Toki, T.: "Abundant expression of erythroid transcription factor p45 NF-E2 mRNA in human peripheral granulocytes" Bicohem. Biophys. Res. Commun.,. (in press). (1996)

Toki, T.：“人外周粒细胞中红系转录因子 p45 NF-E2 mRNA 的丰富表达”Bicohem。