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蛋白质家族。 异聚体转录调节因子，CBF（核心结合因子）。 这个因素 首次研究是作为莫洛尼鼠白血病的调节剂 病毒和多瘤DNA肿瘤病毒的功能。 在哺乳动物中， 造血谱系的发展，以及编码造血干细胞和造血干细胞的基因。 和β亚基是染色体上的常见靶点， 与人类白血病相关的基因重排。 CBFa是DNA结合 蛋白质，而CBFss与α相互作用，增加其DNA结合亲和力。 ss本身不能结合DNA。 (Dr. Banerjee的实验室）和小鼠胚胎干细胞纯合的a CBFss突变功能丧失（Speck博士实验室）。 果蝇研究 将利用Bro、BGB和CBFss基因置于GAL4应答性UAST P中， 元素变换向量。 Gal4表达将由 母体、眼和热休克促进剂。 随着兄弟的孤立 突变后，将检查ss蛋白在 突变拯救实验 如果这是成功的， 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.