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

该项目的目的是建立携带人类白血病易位相关基因或其他癌症相关基因的转基因果蝇系，并利用转基因果蝇鉴定与这些基因发生遗传相互作用的基因。这些研究将为寻找抗白血病或抗癌药物的新靶点奠定基础。在以前的研究中，我建立了携带NPM-MLF 1融合基因的果蝇，该融合基因在髓性发育不良/髓性白血病细胞中发现。我还建立了携带dMLF基因的果蝇，dMLF基因是人类MLF 1基因的果蝇同源物。发现dMLF基因参与Reaper、Hid和Grim诱导的细胞凋亡。在过去的一年中，我发现dMLF与COP 9信号体的亚基dCSN 3相互作用。详细的分析表明，dMLF与dCSN 3的PCI结构域结合，该结构域位于dCSN 3的C-末端区域。此外，还建立了转人组蛋白甲基转移酶G9 a（hG 9a）基因果蝇品系。利用这些果蝇，研究hG 9a基因与异染色质结合蛋白hHP 1 β和γ基因之间的遗传相互作用。

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.