Analysis of recognition mechanisms of misfoled proteins accumulated in the endoplasmic reticulum
| Project/Area Number |
17H01432
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥42,900,000 (Direct Cost: ¥33,000,000、Indirect Cost: ¥9,900,000)
Fiscal Year 2019: ¥12,740,000 (Direct Cost: ¥9,800,000、Indirect Cost: ¥2,940,000)
Fiscal Year 2018: ¥12,740,000 (Direct Cost: ¥9,800,000、Indirect Cost: ¥2,940,000)
Fiscal Year 2017: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
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| Keywords | 構造異常タンパク質 / 認識 / 分解 / 小胞体ストレス応答 / 小胞体関連分解 / 小胞体 / 強制分解 / 認識機構 |
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| Outline of Final Research Achievements |
Protein must gain correct tertiary and quaternary structure to fulfill its function assigned by the genetic code. Misfolded proteins are harmful to the cell. Misfolded proteins accumulated in the endoplasmic reticulum (ER), an organelle, are dealt with ER-associated degradation (ERAD). We unraveled a mechanism of ERAD. In the case of misfolded glycoproteins, the structure of N-glycan is recognized for degradation. We proposed that an enzyme termed EDEN2 initiates the first step of ERAD of misfolded glycoproteins. We demonstrated that EDEM2 indeed catalyzes the first step, only when complexed with TXNDC11 (eLife, 2020).
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| Academic Significance and Societal Importance of the Research Achievements |
EDEM2というタンパク質は、期待される酵素活性を試験管内で発揮しないと2005年に報告されていました。遺伝子破壊細胞の解析により、EDEM2が構造異常糖タンパク質の小胞体関連分解における第一段階に関与することを我々が見出し、従来のモデルを一新する提唱を2014年に行いました。しかし、試験内の結果と細胞内の結果とが矛盾していました。今回、その矛盾を複合体形成の観点を用いて解決しました。小胞体関連分解は６０種以上の疾患の発症に関係しており、これらの治療への道につながる成果です。
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Report
(4 results)
Research Products
(35 results)
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[Journal Article] UPR Transducer BBF2H7 Allows Export of Type II Collagen in a Cargo- and Developmental Stage-Specific Manner2017
Author(s)
Tokiro Ishikawa, Takuya Toyama, Yuki Nakamura, Kentaro Tamada, Hitomi Shimizu, Satoshi Ninagawa, Tetsuya Okada, Yasuhiro Kamei, Tomoko Ishikawa-Fujiwara, Takeshi Todo, Eriko Aoyama, Masaharu Takigawa, Akihiro Harada and Kazutoshi Mori
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Journal Title
Journal of cell biology
Volume: 印刷中
Issue: 6
Pages: 1761-1774
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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