Molecular mechanism of ER stress-induced newly synthesized protein degradation
| Project/Area Number |
18K06222
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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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| Review Section |
Basic Section 44010:Cell biology-related
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| Research Institution | University of Miyazaki |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 小胞体ストレス / タンパク質分解 / 新規合成タンパク質 / タンパク質品質管理 |
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| Outline of Final Research Achievements |
About one-third of all cellular proteins are synthesized in the endoplasmic reticulum (ER). However, unfolded proteins accumulate in the ER due to various environmental factors. To overcome ER stress conditions, cells reduce the accumulation of defective proteins through refolding and ERAD. On the other hand, they prevent protein overload into the ER through translational attenuation and RIDD. Recently, ER stress-induced preemptive quality control (ERpQC) has been reported as a new mechanism to avoid ER overloading. ERpQC is a mechanism to translate and degrade ER-targeted proteins in the cytoplasm. However, the details remain unclear. In this study, we elucidated the molecular mechanism and physiological significance of ERpQC, and defective proteostasis due to its disruption.
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| Academic Significance and Societal Importance of the Research Achievements |
これまでの報告より、リボソームの多くは小胞体膜上や近傍で翻訳を行っており、そこで産生されるタンパク質のうち相当の割合が、不良タンパク質として即座に分解されることが推察される。従って、小胞体膜上での新規合成タンパク質の分解機構を解明することは、真核細胞の機能維持システムさらには、その破綻による病態分子機構の解明に繋がると期待される。本研究で、ERpQCの分子機構ならびにその破綻によるプロテオスタシスの異常を解明したことで、翻訳と共役した新たな分解機構の提唱に繋がり、既知の小胞体品質管理にも新規概念を提示できたという観点から、その生物学的意義は大きい。
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] ER-resident sensor PERK is essential for mitochondrial thermogenesis in brown adipose tissue.2020
Author(s)
Kato H, Okabe K, Miyake M, Hattori K, Fukaya T, Tanimoto K, Beini S, Mizuguchi M, Torii S, Arakawa S, Ono M, Saito Y, Sugiyama T, Funatsu T, Sato K, Shimizu S, Oyadomari S, Ichijo H, Kadowaki H, Nishitoh H.
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Journal Title
Life science alliance
Volume: 3
Issue: 3
Pages: 201900576-201900576
DOI
NAID
Related Report
Peer Reviewed / Open Access
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