| Project/Area Number |
15500256
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Kanazawa University |
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Principal Investigator |
TANIURA Hideo Kanazawa University, Grad Sch Nat Sci Tech, Dept Mol Pharm, Associate Professor, 自然科学研究科, 助教授 (80263325)
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| Co-Investigator(Kenkyū-buntansha) |
YONEDA Yukio Kanazawa University, Grad Sch Nat Sci Tech, Dept Mol Pharm, Professor, 自然科学研究科, 教授 (50094454)
HINOI Eiichi Kanazawa University, Grad Sch Nat Sci Tech, Dept Mol Pharm, Assistant Professor, 自然科学研究科, 助手 (70360865)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Necdin / MAGE-D1 / Msx / E2F1 / p53 / p75NTR / TrkA / NGF / Neuron / cell death / MAGE family / Prader-Willi syndrome / NRAGE |
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| Research Abstract |
Necdin is a 325-amino acid protein encoded in a cDNA clone isolated from a subtraction library of neurally differentiated mouse embryonal carcinoma cells. The mouse necdin gene is expressed predominantly in postmitotic cells such as neuron and skeletal muscle. The human necdin gene is mapped to chromosome 15q11-q12, a region deleted in Prader-Willi syndrome (PWS). Disruption of the mouse necdin gene results in early postnatal lethality, reduction in specific groups of hypothalamic neurons, and be-havioral alterations, which are characteristics of the PWS phenotype. Necdin shows a significant homology to MAGE family proteins, the remarkable feature of which is a large central region termed MAGE homology domain (MHD). We tested the interactions of necdin and MAGE-D1 (a MAGE family protein) with p75NTR (a neurotrophin receptor) by co-immunoprecipitation assay. Both of necdin and MAGE-D1 bound to the intracellular domain of p75NTR. Necdin protects the E2F1-induced cell death using N1E-115 neuroblastoma cells. While MACE-D1 enhances the p75NTR-induced cell death, co-expression of p75NTR significantly abrogated the necdin induced suppression of cell death through the dissociation of the binding between necdin and E2F1. Furthermore, MAGE-D1 dissociated the interaction of TrkA and p75NTR, necdin enhanced the binding. We next investigated the direct interaction of necdin and MAGE-D1. Necdin bound to MACE-D1 through the MAGE homology domain by pull-down assay in vitro and co-immunoprecipitation analysis in vivo. We also demonstrated that necdin interacted with Msx homeoprotein via MAGE-D1. These findings suggest that necdin and MAGE-D1 regulate the neural cell death via the interaction with neurotrophin receptors.
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