MECHANISM OF TRANSFORMATION BY THE V-MYB ONCOGENE

这个项目的目标是理解v-myb

The goal of this project is to understand the mechanism by which the v-myb oncogene of avian myeloblastosis virus (AMV) induces acute myeloid leukemia. This system provides a valuable model for human leukemogenesis for several reasons. First, progenitor of this oncogene, c-myb, is highly conserved in humans, mice and chickens. Second, alterations in c-myb cause myeloid, erythroid, and lymphoid leukemias in mice and birds. Third, c-myb has been shown to amplified and/or rearranged in various human malignancies. The proteins encoded by both v-myb and c-myb are present within the cell nucleus and bind to DNA. Recent work in our laboratory strongly suggests that these myb-encoded nuclear proteins act by regulating the expression of other cellular genes. The studies outlined in this proposal will accomplish the following: (1)Determine if gene regulation by p48v-myb is required for transformation; (2)Define the DNA sequences required for a gene to be regulated by p48v-myb; (3)Determine which domains of p48v-myb are required for gene regulation; (4)Determine the role of phosphorylation and protein-protein interactions in transformation and gene regulation by p48v-myb; (5)Determine the structural and functional conservation of the DNA-binding domains of myb-related proteins from vertebrates, invertebrates, and green plants; (6)Identify and characterize the cellular genes which are controlled by p48v-myb.