Analysis of the mechanism how glycosylation of proteins functions as a signal for ubiquitination
| Project/Area Number |
16K07705
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Applied biochemistry
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
YOSHIDA Yukiko 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, 主席研究員 (90271543)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | ユビキチン / ユビキチンリガーゼ / F-boxタンパク質 / オートファジー / リソソーム / 糖タンパク質 / 小胞体関連分解 / 細胞品質管理 / オルガネラ |
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| Outline of Final Research Achievements |
GGlycoproteins are found in the organelles, on the cell surface, and secreted to out of cells. On the other hand, glycoprotein-specific ubiquitin ligases are present in the cytosol where glycoproteins are not found usually. The endoplasmic reticulum (ER)-associated degradation (ERAD) pathway has been known as an only pathway to appear unfolded glycoproteins in the cytosol. In this study, we found that SCFFBXO27 ubiquitinates exposed glycoproteins normally sequestered on the lumenal surface of organelles, such as lysosomes, following organelle damage, resulting in inducing autophagy for remove the injured organelles.
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| Academic Significance and Societal Importance of the Research Achievements |
生体で合成されるタンパク質のおよそ半数は、糖鎖が付加された糖タンパク質である。糖鎖のタンパク質への付加は膜で囲まれた細胞内小器官（オルガネラ）で行われ、大部分の糖タンパク質は細胞の外に存在する。しかし、糖鎖が存在しないはずの細胞質には、糖鎖を除去する酵素や糖鎖認識ユビキチンリガーゼが存在する。これらの細胞質に存在する糖鎖関連酵素がどのような役割を果たすのかは不明であった。今回の成果は、細胞質に糖鎖が現れることを細胞が危険シグナルとして認知するという、これまで知られていなかった生体防御機構を明らかにしたものである。
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Report
(4 results)
Research Products
(13 results)
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[Journal Article] Ubiquitination of exposed glycoproteins by SCFFBXO27 directs damaged lysosomes for autophagy.2017
Author(s)
Yoshida Y, Yasuda S, Fujita T, Hamasaki M, Murakami A, Kawawaki J, Iwai K, Saeki Y, Yoshimori T, Matsuda N, Tanaka K
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Journal Title
Proc. Natl. Acad. Sci. USA
Volume: 114
Issue: 32
Pages: 8574-8579
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] A comprehensive analysis of SCF complex formation of human F-box proteins.2016
Author(s)
Yoshida, Y., Murakami, A., Kawawaki, J., Saeki, Y, Matsuda, N., Tanaka, K.
Organizer
Cold Spring Harbor Asia conference ‘Ubiquitin family, Autophagy &Diseases’
Place of Presentation
蘇州（中国）
Year and Date
2016-04-04
Related Report
Int'l Joint Research
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