| Project/Area Number |
20390050
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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 |
General anatomy (including Histology/Embryology)
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| Research Institution | Yamagata University |
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Principal Investigator |
GOTO Kaoru 山形大学, 医学部, 教授 (30234975)
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| Co-Investigator(Kenkyū-buntansha) |
ISEKI Ken 山形大学, 医学部, 准教授 (70332921)
HOZUMI Yasukazu 山形大学, 医学部, 准教授 (00372334)
OKADA Masashi 山形大学, 医学部, 講師 (70512614)
TANAKA Toshiaki 山形大学, 医学部, 助教 (70536987)
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| Project Period (FY) |
2008 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000)
Fiscal Year 2011: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2010: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2009: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2008: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
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| Keywords | 細胞周期 / ストレス応答 / 脂質代謝酵素 / アポトーシス / p53 / 核 / プロテアソーム / イノシトールリン脂質 / がん細胞 / 細胞組織化学 / 酸素グルコース欠乏 / 海馬ニューロン / 細胞死 |
|---|
| Research Abstract |
Diacylglycerol kinase (DGK), an enzyme that phosphorylates diacylglycerol to phosphatidic acid, is involved in many pathophysiological cellular responses, such as cancer and apoptosis. Our previous studies show that DGKζ, which contains a nuclear localization signal, is localized in the nucleus of hippocampal neurons but rapidly translocates from the nucleus to the cytoplasm and disappears in the early phase of ischemia, suggesting its implication in an apoptotic process. In this study we investigated the functional link between DGKζ cytoplasmic translocation and p53 that acts as the hub of various stress pathways. We found that cytoplasmic DGKζ induces cytoplasmic localization of p53 after DNA damage and suppresses p53 induction. In neurons, down-regulation of nuclear DGK. after excitotoxic stress leads to aberrant cell cycle reentry, which results in cell death. These findings suggest that DGKζ cytoplasmic translocation exerts distinct effects on signal transduction both in the cytoplasm and the nucleus.
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