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

Research Project

Project/Area Number 12557013
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field General medical chemistry
Research InstitutionKyoto Institute of Technology (2001-2002)
Aichi Cancer Center Research Institute (2000)

Principal Investigator

YAMAGUCHI Masamitsu  Kyoto Institute of Technology, Department of Applied Biology, Professor, 繊維学部, 教授 (00182460)

Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥11,400,000 (Direct Cost: ¥11,400,000)
Fiscal Year 2002: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2000: ¥5,300,000 (Direct Cost: ¥5,300,000)
Keywordsleukemia translocation-related gene / NPM-MLF1 / apoptosis / heterochromatin / histone methyl transferase / transgenic Drosophila / 複製関連遺伝子 / 骨髄性白血病因子 / COP9シグナロソーム / GSTプルダウンアッセイ / PCIドメイン / 遺伝子導入ハエ / dMLF / アポートシス / GAL4-UAS標的発現系 / p53 / crumbs / TAF-Iβ / SET-CAN / armadillo / shotgun
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.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Higashiyama, H.et al.: "Identification of ter94, Drosophila VCP, as a modulator of polyglutamine-induced neurodegeneration"Cell Death and Differentiation. 9. 264-273 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hwang, M.-S.et al.: "The Caudal homeodomain protein activates Drosophila E2F gene expression"Nucleic Acids Res.. 30. 5029-5035 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirose, F.et al.: "Drosophila Mi-2 negatively regulates dDREF by inhibiting its DNA binding activity"Mol. Cell. Biol.. 22. 5182-5193 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kwon, E.et al.: "Transcription control of a gene for Drosophila transcription factor, DREF by DRE and cis-elements conserved between--------------"Gene. 309. 101-116 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagai, Y.et al.: "Prevention of polyglutamine oligomerization and neurodegenera by the peptide inhibitor QBP1 in Drosophila"Hum. Mol. Genet.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 山口政光: "ゲノムの複製と分配(松影昭夫・正井久雄編)"シュプリンガーフェアラーク東京. 145-153 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [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.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamaguchi, M.: "Replication and segregation of genome (Matsukage, A. and Masai, H. ed)"Springer-Verlag Tokyo. 145-153 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Higashiyama, H., et al.: "Identification of ter94, Drosophila VCP, as a modulator of polyglutamine-induced eye degeneration"Cell Death Differ.. 9. 264-273 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hirose, F., et al.: "Drosophila Mi-2 negatively regulates dDREF by inhibiting its DNA binding activity"Mol. Cell. Biol.. 22. 5182-8193 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hwang M.-S., et al.: "The Caudal homeodomain protein activates Drosophila E2F gene expression"Nucleic Acids Res.. 23. 5029-5035 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kwon, E., et al.: "Transcription control of a gene for Drosophila transcription factor, DREF by DRE and cis-elements conserved between Drosophila melanogaster and virilis"Gene. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 山口政光: "ゲノムの複製と分配(松影昭夫・正井久雄編)"シュプリンガー・フエアラーク東京. 234 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Higashiyama, H., et al.: "Identification of fer794, Drosophila VCP, as a modulator of polyglutamine-induced eye degeneration"Cell Death Differ. 9. 264-273 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Crevel, G., et al.: "Nearest neighbour analysis of MCM protein complexes in Drosophila melanogaster"Nucleic Acids Res. 29. 4834-4842 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hirose, F., et al.: "Ectopic expression of DREF induces DNA synthesis, apoptosis and unusual morphogenesis in the Drosophila eye imaginal disc: possible interaction with Plycomb and trihorax group proteins"Mol, Cell. Biol.. 21. 7231-7242 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshida, H., et al.: "Overexpression of DREF in the Drosophila wing imaginal disc induces apoptosis and a notching wing phenotype"Genes to Cells. 6. 1-11 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamaguchi, M., et al.: "Ectopic expression of BEAF32A in the Drosophila eye imaginal disc inhibits differentiation of photoreceptor cells and induces apoptosis"Chromosoma. 110. 313-321 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kwon, E-j., et al.: "Transcriptional regulation of the Drosophila raf proto-oncogene by the transcription factor dE2F"Nucleic Acids Res.. 29. 1808-1814 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Inoue,Y.H., et al.: "Orbit, a novel microtubule-associated protein essential for mitosis in Drosophila."J.Cell Biol.. 149. 153-165 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kwon,E.-J., et al.: "Transcriptional regulation of the Drosophila raf proto-oncogene by D-STAT durimg development and immune response."J.Biol.Chem.. 275. 19824-19830 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Izumi,M., et al.: "Transcription of the catalytic 180-kDa subunit gene of mouse DNA polymerase α is controlled by E2F, and Ets-related ......"Biochem.Biophys.Acta.. 1492. 341-352 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Oshige,M.,, et al.: "Molecular cloning and expression during development of the Drosophila gene for catalvtic subunit of DNA polymerase ε."Gene. 256. 93-100 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohno,K., et al.: "characterization of a Drosophila homologue of the human myelodysplasia/myeloid leukemia factor (MLF)."Gene. 260. 133-143 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kwon,E.-J., et al.: "Transcriptional regulation of the Drosophila raf proto-oncogene by the transcription factor dE2F."Nucleic Acids Res.. (in press). (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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