| Project/Area Number |
17310035
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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 |
Risk sciences of radiation/Chemicals
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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 (10019672)
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| Co-Investigator(Kenkyū-buntansha) |
KAWAI Hidehiko Hiroshima University, Research Institute for Radiation Biology and Medicine, Assistant Professor (30379846)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥15,930,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2007: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2006: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2005: ¥6,000,000 (Direct Cost: ¥6,000,000)
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| Keywords | Apoptosis / Cell cycle / Aurora kinase / Survivin / p53 / Radiation / Cellular response / Ribosome / Aurora / MDM2 / Ribosomal protein / γ線 / 紫外線 / 二次元電気泳動 / 質量分析装置 / プロテオーム解析 / シグナル伝達因子 |
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| Research Abstract |
To isolate and identify the essential signaling mediators responding to radiation, we have searched the proteins regulating signaling pathways between radiation-induced DNA damage and cellular consequences such as cell cycle arrest and apoptotic cell death, and analyzed their functions by proteome techniques. The results obtained for the past 3 years can be summarized as follows.
1. We have examined alteration of the subcellular localization of chromosome passenger proteins (CPPs) including Aurora-B, survivin and INCENP during apoptosis in X-irradiated thymic cells. Aurora-B and survivin were present in detergent insoluble fraction and INCENP cleaved by caspase-3 after radiation exposure, suggesting that the abnormal formation of CPPs complex lead to the induction of apoptosis and chromosome segregation errors.
2. We could identify the RNA methyltransferase NSUN2 as a novel substrate of Aurora-B by proteome analysis, and demonstrated that the Aurora-B participate to regulate the RNA methyltransferase activity via phosphorylation at Ser139 during mitosis.
3. We have analyzed cellular proteins from human leukemic Jurkat cells irradiated with gamma-rays or UV using two dimensional gel electrophoresis (2DE). Among intensive protein spots, acidic ribosomal protein P2 (RpP2) was identified by peptide mass fingerprinting using a mass spectrometry and found that the dephosphorylation of RpP2 may be associated with induction of apoptosis in Jurkat cells by radiation.
4. The results of experiments concerning biological properties of MDM2-MDMX complex suggest that the interaction between MDM2 and MDMX represents a novel mode of p53 regulation.
These results suggest that Aurora kinases and acidic ribosomal proteins in addition to p53 play an important role in radiation-induced signal transduction.
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