FUNCTIONS OF THE BROTHER/CBFB PROTO-ONCOPROTEIN FAMILY

这项拟议的研究涉及两个蛋白质家族，它们相互作用形成一个 异构体转录调节因子CBF(核心结合因子)。这一因素 首次被研究是作为Moloney小鼠白血病的调节剂 病毒和多瘤DNA肿瘤病毒的作用。在哺乳动物中，它是必需的 造血谱系的发展，以及编码A和A的基因 而该因子的ss亚基是染色体上常见的靶标。 与人类白血病相关的重排。CBFA是一种DNA结合 蛋白质，而CBFss与a相互作用，增加其DNA结合亲和力。 SS本身不能结合DNA。 (Banerjee博士的实验室)和在小鼠胚胎干细胞中纯合子 功能丧失CBFss突变(斯派克博士的实验室)。果蝇研究 将利用Bro、Bgb和CBFss基因插入GAL4反应的UAST P 元素变换向量。Gal4表达式将由 母体、眼睛和热休克促进剂。与兄弟的隔绝 突变，将检查ss蛋白的互换性 突变抢救实验。如果成功，嵌合体的研究 蛋白质功能也将被执行。

The proposed study concerns two families of proteins that interact to form a heteromeric transcription regulator, CBF (Core Binding Factor). This factor was first studied in its capacity as a regulator of Moloney murine leukemia virus and Polyoma DNA tumor virus function. In mammals, it is required for the development of hematopoietic lineages, and the genes encoding both the a and ss subunits of the factor are frequent targets for chromosomal rearrangements associated with leukemia in humans. CBFa is a DNA binding protein, while CBFss interacts with a, increasing its DNA binding affinity. ss itself cannot bind DNA. (Dr. Banerjee's lab) and in mouse embryonic stem cells homozygous for a loss of function CBFss mutation (Dr. Speck's lab). The Drosophila studies will utilize Bro, BGB and CBFss genes placed into GAL4-responsive UAST P element transformation vectors. Gal4 expression will be directed by maternal, eye and heat shock promoters. With the isolation of Bro mutations, the ss proteins will be examined for interchangeability in mutation rescue experiments. If that is successful, studies of chimeric protein functions will also be carried out.