| Project/Area Number |
13480168
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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 |
環境影響評価(含放射線生物学)
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
SUZUKI Fumio Hiroshima University, Research Institute for Radiation Biology and Medicine, Professor, 原爆放射線医科学研究所, 教授 (10019672)
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| Co-Investigator(Kenkyū-buntansha) |
YAJIMA Hirohiko Hiroshima University, Research Institute for Radiation Biology and Medicine, Research Associate, 原爆放射線医科学研究所, 助手 (30261895)
TATSUKA Masaaki Hiroshima University, Research Institute for Radiation Biology and Medicine, Associated Professor, 原爆放射線医科学研究所, 助教授 (50216991)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 2003: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2002: ¥4,200,000 (Direct Cost: ¥4,200,000)
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| Keywords | Radiation / Ultraviolet light / Apoptosis / Mitotic checkpoint / Chromosome instability / Mitochondria / Aurora / p53 / γ線 / シグナル伝達 / 細胞応答 / Jurkat / Aurora kinase / cytochrome C / caspase / HeLa / MCF-7 / cytochrome c |
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| Research Abstract |
To elucidate the mechanisms of chromosome instability and apoptosis caused by radiation-induced perturbations in mitotic checkpoint regulations, we have isolated serin/threonine protein kinases that regulate mitotic cell division and analyzed their properties associated with apoptotic cell death. The results obtained for the past 3 years can be summarized as follows:
1. Phosphorylation of histone H3 at Ser-10 is required for maintenance of proper chromosome dynamics during mitosis. We found that exogenous overexpression of Aurora-B kinase AIM-1 in cultured mammalian cells caused increased mitotic Ser-10 phosphorylation with concomitant of lagging chromosomes during mitosis, and that chromosome number instability and increased tumor invasiveness were noted AIM-1 overexpression cell in vivo. These data suggest that increased H3 histone phosphorylation as a result of AIM-1 overexpression is a major precipitating factor of chromosome instability and, thus may play a role in carcinogenesis.
2
… More
. To analyze the mechanism of delayed form of apoptosis that is a common feature of various mammalian cells when irradiated with ionizing radiation, we examined the induction of apoptosis by γ or UV radiation and compared the activation of mitochondrial signaling pathways. The results indicate that delayed or rapid form of apoptosis strongly depend on types of radiation and might be due to the existence of cytosolic factors regulating release of cytochrome c from mitochondria, which functions at the upstream of apoptosis signaling pathways.
3. Since overexpression of Aurora kinase-A and loss of wild-type of p53 function induce similar chromosome instability, which commonly appears in the process of malignant transformation, we have analyzed the relationship between the phosphorylation of Aurora-A and p53 activity. Our data suggest that overexpression of Aurora-A lead to increased degradation of p53, causing downregulation of checkpoint-response pathways and tolerance to apoptotic cells death. Less
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