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2002 Fiscal Year Final Research Report Summary

Genetitc control of programmed cell death in central nervous system

Research Project

Project/Area Number 13480257
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionRIKEN

Principal Investigator

MIURA Masayuki  Lab. Cell Recovery Mechanisms, RIKEN Brain Science Institute Lab. Head, 細胞修復機構研究チーム, チームリーダー (50202338)

Project Period (FY) 2001 – 2002
KeywordsDrosophila / neuron / genetics / cell death / screening
Research Abstract

To discover the cell death triggers encoded in the Drosophila genome, we conducted a misexpression screen using the GAL4/UAS system. The GS vector is a P element-based gene search vector with UAS enhancers (Toba et al., 1999). We crossed a collection of 5,000 lines harboring the GS vector (GS lines) with an eye-specific GAL4 (GMR-GAL4) strain to screen for genes that generated the reduced-eye phenotype. In our large-scale gain-of-function screen, we identified Eiger, the first invertebrate tumor necrosis factor (TNF) superfamily ligand that can induce cell death. Eiger is a type II transmembrane protein with a C-terminal TNF nomology domain. It is predominantly expressed in the nervous system. Genetic evidence shows that Eiger induces cell death by activating the Drosophila JNK pathway. Although this cell death process is blocked by Drosophila inhibitor-of-apoptosis protein 1 (D1AP1), it does not require caspase activity. We also show genetically that Eiger is a physiological ligand for the Drosophila JNK pathway. Our findings demonstrate that Eiger can initiate cell death through an IAP-sensitive cell-death pathway via JNK signaling.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Takemoto, K., Nagai, T., Miyawaki, A., Miura, M: "Spatio-temporal activation of caspase revealed by indicator that is insensitive to environmental effects"J.Cell.Biol.. 160(追記 in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kuranaga, E., Kanuka, H., Igaki, T., Sawamoto, K., Ichijo, H., Okano, H., Mirua, M.: "Reaper-mediated inhibition of DIAP1-induced Drosophila TRAF1 degradation leads to JNK activation"Nature Cell Biol.. 4. 705-710 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeyama, K., Ito, S., Yamamoto, A., Tanimoto, H., Furutani, T., Kanuka, H., Miura, M., Tabata, T., Kato, S.: "Androgen-dependent neurodegeneration by polyglutamine-expnaded human androgen receptor in Drosophila"Neuron. 35. 855-864 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanda, H., Igaki, T., Kanuka, H., Yagi, T., Miura, M.: "Wengen, a member of the Drosophila TNF receptor superfamily, is required for Eiger signaling"J.Biol.Chem.. 277. 28372-28375 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Igaki, T., Kanda, H., Yamamoto-Goto, Y., Kanuka, H., Kuranaga, E., Aigaki, T., Miura, M.: "Eiger, a TNF superfamily ligand that triggers the Drosophila JNK pathway"EMBO J.. 21. 3009-3018 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Igaki, T., Yamamoto-Goto, Y., Tokushige, N., Kanda, H., MIura, M.: "Downregulation of DIAP1 triggers a novel Drosophila cell death pathway mediated by DARK and DRONC"J.Biol.Chem.. 277. 23103-23106 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takemoto, K., Nagai, T., Miyawaki, A., and Miura, M.: "Spatio-temporal activation of caspase revealed by indicator that is insensitive to environmental effects"J. Cell Biol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kuranaga, E., Kanuka, H., Igaki, T., Sawamoto, K., Ichijo, H., Okano, H., and Miura, M.: "Reaper-mediated inhibition of DIAP1-induced Drosophila TRAF1 degradation leads to JNK activation"Nature Cell Biol.. 4. 705-710 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeyama, K., Ito, S., Yamamoto, A., Tanimoto, H., Furutani, T., Kanuka, H., Miura, M., Tabata, T., and Kato, S. :: "Androgen-dependent neurodegeneration by polyglutamine-expanded human androgen receptor in Drosophila"Neuron. 35. 855-864 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kanda, H., Igaki, T., Kanuka, H.,Yagi, T., and Miura, M.: "Wengen, a member of the Drosophila TNF receptor superfamity, is required for Eiger signaling"J. Biol. Chem.. 277. 28372-28375 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Igaki, T.,Kanda, H., Yamamoto-Goto, Y., Kanuka, H., Kuranaga, E., Aigaki, T., and Miura, M.: "Elger, a TNF superfamily ligand that triggers the Drosophila JNK pathway"EMBO J.. 21. 3009-3018 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Igaki, T., Yamamoto-Goto, Y.,Tokushige, N., Kanda, H., Miura, M.: "Downregulation of DIAP1 triggers a novel Drosophila cell death pathway mediated by DARK and DRONC"J. Biol. Chem.. 277. 23103-23106 (2002)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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