2002 Fiscal Year Final Research Report Summary
Comprehensive studies on establishment of transgenic flies carrying human cancer-related gene for searching anti-cancer drugs and its molecular targets
| Project/Area Number |
12557013
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
General medical chemistry
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| Research Institution | Kyoto Institute of Technology (2001-2002)
Aichi Cancer Center Research Institute (2000) |
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Principal Investigator |
YAMAGUCHI Masamitsu Kyoto Institute of Technology, Department of Applied Biology, Professor, 繊維学部, 教授 (00182460)
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| Project Period (FY) |
2000 – 2002
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| Keywords | leukemia translocation-related gene / NPM-MLF1 / apoptosis / heterochromatin / histone methyl transferase / transgenic Drosophila |
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| Research Abstract |
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.
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[Publications] Higashiyama, H., Hirose, F., Yamaguchi, M., lnoue, Y. H, Fujikake, N., Matsukage, A., Kakizuka, A,: "Identification of ter94, Drosophila VCP. as a modulator of polyglutamine-induced neurodegeneration"Cell Death and Differentiation. 9. 264-273 (2002)
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[Publications] Hwang, M.-S., Kim, Y.-S., Choi, N.-H., Park, J.-H, , Oh, E.-J., Kwon, E.-J., Yamaguchi, M., Yoo, M.-A.: "The Caudal homeodomain protein activates Drosophila E2F gene expression"Nucleic Acids Res.. 30. 5029-5035 (2002)
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[Publications] Hirose, F., Ohshima, N., Kwon, E.-J, , Yoshida, H., Yamaguchi, M.: "Drosophila Mi-2 negatively regulates dDREF by inhibiting its DNA-binding activity"Mol. Cell. Biol.. 22. 5182-5193 (2002)
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[Publications] Kwon, E, ., Seto, H., Hirose, F., Ohshima, N., Takahashi, Y., Nishida, Y., Yamaguchi, M.: "Transcription control of a gene for Drosophila transcription factor. DREF by DRE and cis-elements conserved between Drosophila melanogaster and virilis"Gene. 309. 101-116 (2003)
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[Publications] Nagai, Y, , Fujikake, N., Ohno, K., Higashiyama, H., Popi H. A., Rahadian, J., Yamaguchi, M., Strittmater, W. J., Burke, J. R., Toda, T.: "Prevention of polyglutamin oligomerization and neurodegeneration by the peptide inhibitor QBP1 in Drosophila"Hum. Mol. Genet.. in press.
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