| Project/Area Number |
08278102
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Research Institution | Tokyo Metropolitan Institute of Gerontology (2000)
The University of Tokyo (1996-1999) |
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Principal Investigator |
SUZUKI Koichi Tokyo Metropolitan Institute of Gerontology, Director, 所長 (80011948)
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| Co-Investigator(Kenkyū-buntansha) |
MURAKAMI Yasuko Jikei University School of Medicine, Professor, 医学部, 教授 (30056709)
YAMAO Fumiaki National Institute of Genetics, Associate Professo, 助教授 (10158074)
TANAKA Keiji Tokyo Metropolitan Institute of Medical Science, Laboratory Chief, 部長(研究職) (10108871)
MAKI Masatoshi Graduate School of Bioagricultural Sciences, Nagoya University, Professor, 大学院・生命農学研究科, 教授 (40183610)
KIDO Hiroshi Institute for Enzyme Research, University of Tokushima, Professor, 分子酵素学研究センター, 教授 (50144978)
佐方 功幸 九州大学理学部, 教授 (80142024)
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| Project Period (FY) |
1996 – 1999
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥334,600,000 (Direct Cost: ¥334,600,000)
Fiscal Year 1999: ¥61,800,000 (Direct Cost: ¥61,800,000)
Fiscal Year 1998: ¥57,600,000 (Direct Cost: ¥57,600,000)
Fiscal Year 1997: ¥95,400,000 (Direct Cost: ¥95,400,000)
Fiscal Year 1996: ¥119,800,000 (Direct Cost: ¥119,800,000)
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| Keywords | Proteolysis / Protein Degradation / Proteases / Proteasome / Calpain / Ornithine Decarboxylase / X線解析 / トリプターゼ / バイオモジュレーター |
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| Research Abstract |
To analyze mechanisms for selective intracellular protein degradation, two major protease systems in cells, proteasome and calpain, were mainly studied. Suzuki succeeded to analyze the crystal structure of calpain at 2.3Å and found that calpain exists as an inactive proenzyme which requires Ca-induced large conformational changes to become active. Domain III of unknown function is responsible for the Ca-induced conformational changes and translocation to biological membrane. Maki identified 4 novel calpastatin species produced by alternative splicing. Tanaka identified 5 alternative splicing variants of poly-ubiquitin receptor of 26S proteasome differently expressed in various tissues and thus showed distinct functions. A novel proteasome species responsible for endogenous antigen processing containing catalytic and regulatory subunits distinct from 26S proteasome was discovered and named immune proteasome. Further, the gene product for Parkinsonism was identified to be ubiquitin ligase suggesting that the deposition of its target protein of the ligase would be the cause of the disease. Yamao identified a novel proteolytic system of fission yeast for degradation of M phase cyclin containing novel E2. Murakami clarified the molecular mechanism for binding and degradation of ornithine decarboxylase by proteasome and the function of antizyme and ATP in the process. Kido analyzed molecular basis for influenza virus infection to host cells that requires specific degradation of virus membrane proteins by host cell tryptase clara. A specific inhibitor protein for clara tryptase was also fund.
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