| Project/Area Number |
13480257
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | RIKEN |
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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)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2002: ¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 2001: ¥7,800,000 (Direct Cost: ¥7,800,000)
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| Keywords | Drosophila / neuron / genetics / cell death / screening |
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| 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.
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