| Project/Area Number |
03102006
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| Research Category |
Grant-in-Aid for Specially Promoted Research
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| Allocation Type | Single-year Grants |
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| Research Institution | Institute for Enzyme Research, The University of Tokushima |
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Principal Investigator |
ICHIHARA Akira Department Enzyme Pathology, The University of Tokushima, Professor, 酵素科学研究センター, 教授 (40035374)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Keiji Department Enzyme Pathology, The University of Tokushima, Assistant Professor, 酵素科学研究センター, 助手 (10108871)
YOSHIMURA Tetsuro Department of Enzyme Regulation, The University of Tokushima, Associate Professo, 酵素科学研究センター, 助教授 (30035472)
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| Project Period (FY) |
1991 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥170,000,000 (Direct Cost: ¥170,000,000)
Fiscal Year 1993: ¥20,000,000 (Direct Cost: ¥20,000,000)
Fiscal Year 1992: ¥50,000,000 (Direct Cost: ¥50,000,000)
Fiscal Year 1991: ¥100,000,000 (Direct Cost: ¥100,000,000)
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| Keywords | Proteasome / Ubiquitin / Energy-dependent proteolysis / Cell cycle / Antigen Processing / Supramolecular complex / Gamma-interferon / MHC classI-restricted antigen presentation / エネルギー依存性蛋白分解 / MHCクラスI拘束性抗原提示 / 多機能プロテアーゼ複合体 / 遺伝子転写制御機構 / 細胞内蛋白質分解機構 / 抗原プロセシング・提示 / 分子適合 / エネルギー依存性分子識別 / 蛋白質超分子複合体 / プロテアソ-ム / 多機能プロテア-ゼ複合体 / エネルギ-依存性分子識別 / 細胞増殖・分化 |
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| Research Abstract |
(1) Structural Analysis of Proteasomes at the Molecular Level : We demonstrated that proteasomes are found as two isoforms in cells. One is the ATP-independent 20S form and the other is an ATP-dependent 26S form. Various physical analyzes showed that molecular masses of these two forms are determined to be approximately 750 kDa and 2000 kDa, respectively. The primary structures of 7 alpha-type and 9 beta-type subunits of the 20S proteasome complex in human, rat and yeast were determined by their cDNA cloning. Based on the homology analysis, we proposed the novel term "the proteasome gene family" for these highly homologous gene groups. Furthermore, we have prepared the large crystals of the bovine 20S proteasome and carried out its preliminary X-ray analysis. By electron microscopy, we proposed the "caterpillar-shape" model for the 26S proteasome, consisting of approximately 50 non-identical subunits. The 26S proteasome was found to be the unusually large supra-molecular complex.
(2) Molecular Functions of Proteasomes : The 26S proteasome was demonstrated to be an ATP-dependent protease catalyzing selective degradation of target proteins conjugated with multiple ubiquitins as the degradation signal. Moreover, we found for the first time that ornithine decarboxylase, a most short-lived enzyme in cells responsible for biosynthesis of polyamines, was degraded ATP-dependently by the 26S proteasome without ubiquitination.
(3) Physiological Functions of Proteasomes : The 26S proteasome degraded various nuclear oncoproteins, such as Mos, Fos and Myc, closely related with cell cycle progression in an ATP-, ubiquitin-dependent fashion, suggesting possible involvement of the proteasome in cell cycle regulation. In addition, we found that gamma-interferon induced proteasomes with different subunit organizations for acquirement of the functional diversity and suggested that proteasoms play an essential role for the MHC class-I restricted antigen processing pathway.
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