2020 Fiscal Year Final Research Report
Construction of DUB MAP for innate immune and inflammatory responses
Project/Area Number |
19K22541
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 49:Pathology, infection/immunology, and related fields
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Research Institution | Osaka City University |
Principal Investigator |
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Project Period (FY) |
2019-06-28 – 2021-03-31
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Keywords | 脱ユビキチン化酵素 / タンパク質 / 細胞 / 炎症 / 自然免疫 / オートファジー |
Outline of Final Research Achievements |
Protein ubiquitination was identified as a marker that binds to proteins in cells and selectively leads to proteasomal degradation. The discoverers of protein ubiquitination is awarded to the Nobel Prize in Chemistry in 2004, due to the importance of cellular functions. Subsequent studies have shown that it is involved in various cell functions, such as inflammation and immune signals, selective autophagy, DNA repair, and proteolysis. There are about 100 types of deubiquitinating enzymes (DUBs) in humans that cleave ubiquitin chains and control various cell functions. In this study, we prepared 88 types of DUBs comprehensively investigated the characteristics of DUBs involved in inflammation / immune signals and selective autophagy, and proceeded with the DUB inhibitors.
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Free Research Field |
病態医化学
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Academic Significance and Societal Importance of the Research Achievements |
ユビキチン修飾系の制御破綻は癌や神経変性疾患など各種疾患発症に関わるため、近年、脱ユビキチン化酵素(DUB)が創薬標的として高く注目されている。我々は独創的にDUBのライブラリーを調整し、各種細胞機能を制御するDUBの抽出を進め、特に炎症応答に関わる新規DUBを見出すことができた。また、細胞内侵入細菌が引き起こす選択的オートファジーとの関連、及び直鎖状ユビキチンを特異的に分解するDUBに対する阻害剤探索を行なった。これらの研究から新規細胞制御性DUBの発見と創薬シーズ展開が期待できる。
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