The Role of stress proteins in the aggregation and cytotoxicity of polyglutamine
| Project/Area Number |
13210155
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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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| Review Section |
Biological Sciences
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| Research Institution | Tokyo Metropolitan Organization for Medical Research |
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Principal Investigator |
KIMURA Yoko Tokyo Metropolitan Institute of Medical Science, Researcher, 東京都臨床医学総合研究所, 研究員 (80291152)
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| Co-Investigator(Kenkyū-buntansha) |
KAKIZUKA Akira Kyoto University, Graduate school of Biostudies, Professor, 大学院生命科学研究科, 教授 (80204329)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥30,000,000 (Direct Cost: ¥30,000,000)
Fiscal Year 2002: ¥12,000,000 (Direct Cost: ¥12,000,000)
Fiscal Year 2001: ¥18,000,000 (Direct Cost: ¥18,000,000)
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| Keywords | polyglutamine / neurodegerative disease / molecular chaperone / amyloid / AAA superfamily protein / aggregates / Hsp104 / VCP / p97 / AAA+ スーパーファミリー蛋白質 / 神経変性疾患 / コンフォーメーション / 構造変換 / コンフォーメーション病 / 酵母 |
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| Research Abstract |
The polyglutamine diseases are caused by the expression of expanded unstable CAG repeats that code for polyglutamine in the responsible genes. These diseases are recognized as a type with a conformationally abnormal or amyloid-related proteins. We identified VCP/p97, one of AAA^+ superfamily proteins, that directly binds to polyglutamine in vitro, and that functions as an enhancer of neurodegeration by polyglutamine expressed in a fly model. We also found that vacuolar formation is one of hallmarks followed by cell death by the expression of polyglutamine in cultured cell systems. Hsp104, another member of AAA^+ superfamily proteins, is required for aggregate formation of polyglutamine expressed in yeast. As polyglutamine takes a form of amyoid in various systems, these results suggest a possibility that some molecular chaperones facilitate amyloid formation of polyglutamines. We further investigated how these molecular chaperones work on polyglutamine. We found that a certain amount of pre-existing polyglutamine aggregates are required for Hsp 104 to enhance the polyglutamine aggregation.
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Report
(3 results)
Research Products
(23 results)
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[Publications] Matsumoto S, Tanaka E, Nemoto T, Ono T, Takagi T, Imai J, Kimura.Y, Yahara, I., Kobayakawa T, Ayuse T, Oi K, Mizuno A: "Interaction between the N-terminal and middle regions is essential for the in vivo function of HSP90 molecular chaperone"J.Biol.Chem.. 277. 34959-34966 (2002)
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