2020 Fiscal Year Final Research Report
Elucidating the role of branched ubiquitin code
| Project/Area Number |
17H03986
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Hoshi University (2019-2020)
Tokyo Metropolitan Institute of Medical Science (2017-2018) |
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Principal Investigator |
Ohtake Fumiaki 星薬科大学, 先端生命科学研究所, 特任准教授 (60447373)
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| Co-Investigator(Kenkyū-buntansha) |
土屋 光 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 主任研究員 (90760132)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Keywords | ユビキチン / 標的タンパク質分解 / プロテアソーム / アポトーシス / PROTAC |
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| Outline of Final Research Achievements |
Post-translational modification of proteins with ubiquitin regulates numerous biological pathways such as proteasomal protein degradation, inflammation, and DNA repair. However, how different ubiquitin signals are integrated to govern complex biological outputs remains largely unknown. In this study, we identified UBR5 and TRIP12 as ubiquitin chain branching factors. UBR5 modifies TXNIP with K48/K63 branched ubiquitin chains to promote its proteasomal degradation.
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| Free Research Field |
タンパク質分解
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によって、分岐型ユビキチン鎖がタンパク質分解を促進することが明らかとなり、その責任酵素の一端を解明した。ユビキチン修飾系の異常は様々な疾患の原因となっており、ユビキチン化の詳細なメカニズムの解明は、将来的に、疾患発症機構の解明につながる可能性が期待される。
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