FUNCTIONS OF THE BROTHER/CBFB PROTO-ONCOPROTEIN FAMILY

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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.