TRIM-SUMO-11S proteasome pathway: a possible axis for ubiquitylation-independent endoplasmic reticulum-associated degradation of AE1 mutants
| Project/Area Number |
16H05031
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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 |
Veterinary medical science
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| Research Institution | Hokkaido University |
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Principal Investigator |
INABA Mutsumi 北海道大学, 獣医学研究院, 教授 (00183179)
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| Co-Investigator(Kenkyū-buntansha) |
高田 健介 北海道大学, 獣医学研究院, 准教授 (40570073)
山崎 淳平 北海道大学, 獣医学研究院, 助教 (20732902)
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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 |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2018: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2016: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
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| Keywords | 小胞体関連分解 / 膜タンパク質 / プロテアソーム / ユビキチン / SUMO / シャペロン / 疾患 / 品質管理 / 変異タンパク質 / 膜蛋白質 / ユビキチン非依存性 |
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| Outline of Final Research Achievements |
The ER-associated degradation (ERAD) of R664X AE1 is characteristic because it appears to occur on the ER membrane in a ubiquitylation-independent manner. The TRIM-SUMO-11S pathway was alternative for the ERAD of R664X AE1. However, the present study demonstrated that SUMOylation and TRIM family proteins including TRIM28 had no essential roles in the ERAD of R664X AE1. The present study also showed that the cytoplasmic domain of AE1 was important in dislocation through the dislocon Derlins and recognition/degradation by 26S proteasomes.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、様々な疾患病態、抗原提示、あるいはプロテアソームの構造解析から、小胞体関連分解の仕組みとして、従来のUb-26Sプロテアソーム系に加えて新たにUb非依存性プロテアソームの普遍性が認識されている。R664X AE1のUb非依存性小胞体関連分解の仕組みの解明は、その先駆けとして、多様な疾患や小胞体機能異常が関わる疾患の病態・治療法研究の基盤を築く独創的な学術的意義と社会的有用性をもつ。
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Report
(4 results)
Research Products
(1 results)
