| Project/Area Number |
17K13258
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biomolecular chemistry
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| Research Institution | Hokkaido University |
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Principal Investigator |
KATO IZUMI 北海道大学, 薬学研究院, 助教 (40634994)
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| Project Period (FY) |
2017-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 酸化ストレス / DJ-1 / p53 / 分子間相互作用 / パーキンソン病 / 癌 |
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| Outline of Final Research Achievements |
Parkinson's disease causative factor DJ-1 changes the oxidation valence of its cys106 stepwise after oxidation. However, since molecular protein research focusing on the oxidation valence and cell biology research on determining protein binding and cell death were conducted separately. Therefore, the mechanism of binding protein selection according to the oxidation valence of DJ-1 and the death control mechanism of nerve cells was not clear. We prepared a constitutively oxidized DJ-1 mutant and a constitutively reduced DJ-1 mutant, evaluated their p53-binding ability, and investigated the effect of suppressing nerve cell death, thereby revealed the mechanism by which the function changes in response to the oxidation of DJ-1 cys106 at the molecular and cellular levels.
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| Academic Significance and Societal Importance of the Research Achievements |
パーキンソン病発症機序を解明するためには、酸化ストレスによるドパミン作動性神経細胞死が、酸化ストレス後のどの反応によって起こるのか明らかにすることが重要である。ここでは、パーキンソン病原因因子DJ-1がシステイン106残基の酸化型でのみ、p53と結合し、神経細胞死を抑制することを相互作用解析、細胞活性化測定から明らかにした。従来のDJ-1変異体とは異なり、DJ-1システイン106残基のチオール基を保持した恒常的還元型DJ-1変異体を作製したことで、DJ-1の酸化型と還元型の機能の違いを明確に分けることができるようになったことは、発症メカニズム解明のためにも非常に有用である。
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