Comprehensive studies on establishment of transgenic flies carrying human cancer-related gene for searching anti-cancer drugs and its molecular targets

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The purpose of the project is to establish transgenic Drosophila lines carrying human leukemia translocation-related genes or other cancer-related genes and to identify genes that genetically interact with these genes by utilizing the transgenic flies. The studies will establish basis for searching novel targets for anti-leukemia or anti-cancer drugs. In the previous studies, I established flies carrying NPM-MLF1 fusion gene that was found in meylodysplasia/myeloid leukemia cells. I have also established flies carrying dMLF gene, a Drosophila homologue of the human MLF1 gene. The dMLF gene was found to be involved in apoptosis which was induced by Reaper, Hid and Grim. In the past year, I have found that dMLF interacts with dCSN3, a subunit of the COP9 signalosome. The detailed analyses have revealed that dMLF binds to PCI domain of dCSN3 that is located in C-terminal region of dCSN3. In addition, the transgenic Drosophila lines carrying the gene for human histone methyl transferase G9a (hG9a) were established. By utilizing these flies, genetic interaction between hG9a gene and heterochromatin-binding protein hHP1β and γ genes will be examined.