New classification of infantile leukemia using lineage-specific transcription

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，对红细胞特异性基因表达和血小板形成的调节至关重要。为了表征人类p18，我们分离了编码Maf家族小蛋白MafK和MafG的人类cdna。mafK基因和mafG基因编码的蛋白分别由156和162个氨基酸残基组成，这些蛋白的分子量约为18kDa。MafK和MafG含有一个基本的DNA结合域和一个亮氨酸拉链，缺乏假定的反式激活子域。推导出的人MafK或鸡MafG氨基酸序列与推定的鸡MafK或鸡MafG氨基酸序列具有93%的一致性。细菌表达的MafK和MafG蛋白与p45形成异源二聚体，能有效结合NF-E2探针。Maf小蛋白的同型二聚体也与NF-E2探针结合。然而，p45/小Maf异二聚体与NF-E2探针的结合比小Maf同二聚体更突出。在瞬时转染实验中，在p45存在的情况下，小Mafs激活NF-E2位点依赖的报告基因的转录，而在p45缺失的情况下，小Mafs抑制转录。迄今为止，在所有检测的人体组织中都检测到MafK和MafG的mrna。在心脏、骨骼肌和胎盘中，mafK转录本的水平相对较高。mafG转录本的水平在组织间变化较小。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，人类小maff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。

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.