Functions of the runt gene family in development

PEBP2转录因子的功能是由α和β亚基组成的异源二聚体。α亚基负责PEBP2的DNA结合活性，这一活性通过与β亚基的相互作用而进一步增强。AML1基因编码PEBP2的α亚基，与果蝇矮小基因在哺乳动物中的同源物相对应，果蝇矮小基因参与果蝇的分割、神经发育和性别决定。哺乳动物的PEBP2β基因编码PEBP2的β亚基，代表矮小伙伴基因。AMI.I和PEBP2beta基因都参与了与人类急性髓系白血病相关的染色体重排。由于易位和/或倒位，产生了嵌合基因。本研究旨在揭示哺乳动物矮小及其伴侣基因在细胞分化、转化和发育中的功能。研究结果总结如下：1)PEBP2转录因子对于胚胎主动脉-性腺-中肾区域的造血发育是必不可少的，并且以剂量依赖的方式发挥作用。2)与人AML相关的涉及PEBP2β基因的嵌合基因的产物损害了细胞质骨架的结构。3)AML1转录因子的剂量在决定T细胞受体介导的细胞生存或细胞死亡信号的质量方面至关重要。

The PEBP2 transcription factor functions as a heterodimer composed of the alpha and beta subunits. The alpha subunit is responsible for the DNA binding activity of PEBP2, which is furthermore enhanced by interacting with the beta subunit. The AML1 gene, encoding the alpha subunit of PEBP2, corresponds to the mammalian homologue of Drosophila runt gene, a gene involved in Segmentation, neural development and sex determination in fly. The mammalian PEBP2beta gene encoding the beta subunit of PEBP2 represents a runt-partner gene. Both the AMI.I and PEBP2beta genes are involved in chromosomal rearrangements associated which human acute myeloid leukemia. As a result of translocation and/or inversion, the chimeric genes are generated.The study was carried out to reveal the functions of mammalian runt and runt-partner genes in cell differentiation, transformation and development. The results are summarized as follows.l)The PEBP2 transcription factor is indispensable and functions in a dose dependent manner for the hematopoietic development in the embryonic aorta-gonad-mesonephros region.2)The product of the chimeric gene associate with human AML and involving the PEBP2beta gene impairs the architecture of cytoplasmic cytoskeleton.3)A dose of AML1 transcription factor is critical in deternuning the quality of T cell receptor-mediated signal to cell survival or cell death.