Mechanisms of protein disulfide bond formation in the ER of mammalian cells
Project/Area Number |
15K07381
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Applied biochemistry
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Research Institution | Tohoku University |
Principal Investigator |
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Project Period (FY) |
2015-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | ジスルフィド結合 / 哺乳動物 / 膵臓 / 分泌タンパク質 / 小胞体 / PDI / 物質生産 |
Outline of Final Research Achievements |
Formation of disulfide bonds is a crucial step in the folding of a huge number of secretory proteins. The ER of mammalian cells houses twenty PDI family members, which are supposed to catalyze disulfide bond formation in secretory proteins. PDIp is a PDI family member predominantly expressed in the pancreas. Here, we show that PDIp interacts directly with a number of digestive enzymes in vivo and assists in the folding of one of these enzymes, leading to our proposal that PDIp is a PDI family member dedicated to the folding of pancreatic digestive enzymes. Furthermore, we show that IRE1α, an ER stress sensor, plays a crucial role in the production of insulin by upregulating the biosynthesis of some PDI family members. These findings provide new insights into the disulfide bond formation system of mammalian cells.
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Academic Significance and Societal Importance of the Research Achievements |
本研究で、私達は、膵臓で作られる消化酵素のうちのエラスターゼと呼ばれるタンパク質分解酵素が正しい立体構造に折り畳まれる過程で必要な新規の因子PDIpを発見しました。マウスの膵臓を調べたところ、PDIpは、エラスターゼ以外にも、トリプシン、キモトリプシン、α-アミラーゼなど膵臓で作られる様々な消化酵素に作用することが分かりました。よって、これらの消化酵素が正しい立体構造に折り畳まれる過程でもPDIpは働いている可能性があります。本研究から得られる知見は、将来的には、膵臓に関連する病気の原因の解明やヒト由来の消化酵素を微生物や動物細胞の培養によって生産させる際に役立つと期待されます。
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Report
(5 results)
Research Products
(33 results)
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[Presentation] Physiological substrates of PDIp, a pancreas-specific protein disulfide isomerase family member protein2018
Author(s)
Takushi Fujimoto, Orie Nakamura, Michiko Saito, Akio Tsuru, Masaki Matsumoto, Kenji Kohno, Kenji Inaba, Hiroshi Kadokura
Organizer
FASEB conference Protein Folding in the Cell, Olean, NY, USA
Related Report
Int'l Joint Research
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[Presentation] Physiological function of PDIp, a pancreas-specific protein disulfide isomerase family member protein2018
Author(s)
Takushi Fujimoto, Orie Nakamura, Michiko Saito, Akio Tsuru, Masaki Matsumoto, Kenji Kohno, Kenji Inaba, Hiroshi Kadokura
Organizer
5th CWRU-Tohoku Joint Workshop, Sendai, Japan
Related Report
Int'l Joint Research
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[Presentation] Elucidation of physiological function of PDIp, a pancreas-specific protein disulfide isomerase family member protein2018
Author(s)
Takushi Fujimoto, Orie Nakamura, Michiko Saito, Akio Tsuru, Masaki Matsumoto, Kenji Kohno, Kenji Inaba, and Hiroshi Kadokura
Organizer
International Symposium on“Proteins; from the Cradle to the Grave”, Shiga, Japan
Related Report
Int'l Joint Research
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