2001 Fiscal Year Final Research Report Summary
ANALYSES OF THE TRANSCRIPTIONAL REGULATORY NETWORK FOR DROSOPHILA DNA REPLICATION GENES
| Project/Area Number |
11480217
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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 | 一般 |
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| Research Field |
Cell biology
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| Research Institution | AICHI CANCER CENTER |
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Principal Investigator |
YAMAGUCHI Masamitsu AICHI CANCER CENTER, RESEARCH INSTITUTE DIVISION OF BIOCHEMISTRY, SECTION HEAD, 発がん制御研究部, 室長 (00182460)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUKAGE Akio JAPAN WOMEN'S UNIVERSITY, FACULTY OF SCIENCE, PROFESSOR, 理学部, 教授 (90019571)
INOUE Yoshihiro KYOTO INSTITUTE OF TECHNOLOGY, DROSOPHILA RESEARCH CENTER, LECTURER, ショウジョウバエ遺伝資源センター, 講師 (90201938)
HIROSE Fumiko AICHI CANCER CENTER, RESEARCH INSTITUTE DIVISION OF BIOCHEMISTRY, SENIOR RESEARCHER, 発がん制御研究部, 主任研究員 (60208882)
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| Project Period (FY) |
1999 – 2000
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| Keywords | DROSOPHILA / PCNA / RFX / DNA replication-related genes / Chromatin remodling factor / Mi-2 / DREF |
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| Research Abstract |
We have identified a novel transcriptional regulatory element, PRE (positive regulatory element) located between URE (upstream regulatory element) and DRE (DNA replication-related element) in the Drosophila PCNA (proliferating cell nuclear antigen) gene. One-hybrid screening using the PRE sequence as a bait allowed us to clone a CDNA encoding a novel transcription factor carrying the RFX domain. The factor was named as Drfx2 (Drosophila RFX2). Over expression of DNA-binding domain of this factor induced the abnormal eye morphology (rough eye phenotype) hi adult flies. Since the human RFX protein is reported to be involved in regulation of the human PCNA gene, function of RFX family protein may be conserved between mammal and Drosophila.
We have also identified Mi-2, a chromatin remodeling factor as an interactant of the transcription factor DREF that coordinately regulates DNA replication related genes in Drosophila. Over-expression of DREF in eye imaginal discs induces ectopic DNA synthesis and apoptosis in eye disc cells and consequently the adult flies exhibit the rough eye phenotype. Half reduction of the Mi-2 gene dose strongly enhanced the DREFinduced rough eye phenotype, suggesting that Mi-2 negatively regulates the function of DREF in vivo. In consistent with this, the purified GST-Mi-2 fusion protein inhibits DNA-binding activity of DREF in vitro.
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[Publications] Yamaguchi, M., Hirose, F., Inoue, Y.H., Shiraki, M., Hayashi, Y., Nishii, Y. and Matsukage, A.: "Ectopic expression of human p53 inhibits entry into S-phase and induces apoptosis in the Drosophila eye imaginal disc."Oncogene. 18. 6767-6775 (1999)
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[Publications] Hayashi, Y., Yamaguchi, M., Nishimoto, Y., Taguchi, O., Matsukage, A. and Yamaguchi, M.: "A binding site for the transcription factor Grainyhead/NTF-1 contributes to regulation of the Drosophila proliferating cell nuclear antigen promoter"J. Biol. Chem.. 274. 35080-35088 (1999)
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[Publications] Inoue, Y.H., do Carmo Avides, M., Shiraki, M., Deak, P., Avides, M.C., Yamaguchi, M., Nishimoto, Y., Matsukage, A. and Glover, D.M.: "Orbit, a novel microtubule-associated protein essential for mitosis in Drosophila"J. Cell Biol.. 149. 153-165 (2000)
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[Publications] Kwon, E.-J., Park, H.-S., Kim, Y.-S., Oh, E.-J., Nishida, Y., Matsukage, A., Yoo, M.-A. and 75 Yamaguchi, M.: "Transcriptional regulation of the Drosophila raf proto-oncogene by D-STAT during development and immune response"J. Biol. Chem. 275. 19824-19830 (2000)
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[Publications] Izumi, M., Yokoi, M., Nishikawa, N.S., Miyazawa, H., Sugino, A., Yamagishi, M., Yamaguchi, M., Matsukage, A., Yatagai, F. and Hanaoka, F.: "Transcription of the catalytic 180-kDa subunit gene of mouse DNA polymerase α is controlled by E2F, and Ets-related transcription factor, and Sp1. Biochem."Biophys. Acta.. 1492. 341-352 (2000)
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[Publications] Oshige, M., Yoshida, H., Hirose, F., Takata, K., Inoue, Y.H., Aoyagi, N., Yamaguchi, M., Koiwai, O., Matsukage, A. and Sakaguchi, K.: "Molecular cloning and expression during development of the Drosophila gene for the catalytic subunit of DNA polymerase e"Gene. 256. 93-100 (2000)
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[Publications] Ohno, K., Takahashi, Y., Hirose, F., Inoue, Y.H., Taguchi, O., Nishida, Y., Matsukage, A. and Yamaguchi, M.: "Characterization of a Drosophila homologue of the human myelodysplasia/myeloid leukemia factor (MLF)"Gene. 260. 133-143 (2000)
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[Publications] Kwon, E.-J., Oh, E.-J., Kim, Y.-S., Hirose, F., Ohno, K., Nishida, Y., Matsukage, A., Yamaguchi, M. and Yoo. M.-A.: "Transcriptional regulation of the Drosophila raf proto-oncogene by the transcription factor dE2F"Nucleic Acids Res.. 29. 1808-1814 (2001)
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