Identification of novel enzymes for C-mannosylation and analysis of its substrate proteins
| Project/Area Number |
18K06137
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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 43030:Functional biochemistry-related
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| Research Institution | Keio University |
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Principal Investigator |
Simizu Siro 慶應義塾大学, 理工学部(矢上), 教授 (30312268)
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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: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | C型糖修飾 / R-spondin2 / MFAP4 / ADAMTS4 / Isthmin-1 / 細胞外分泌 / フィブリノーゲンC末端領域 / がん分子標的 |
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| Outline of Final Research Achievements |
The objective of the research is to identify the enzyme responsible for C-mannosylation and to search for new substrate proteins. During the period, we were able to develop a simple method for detecting C-mannosylation to identify the responsible enzyme(s). Furthermore, we identified R-spondin2, MFAP4, ADAMTS4 and Isthmin-1 as novel C-mannosylated proteins. Functional analysis of each substrate protein was also performed, and it was demonstrated that C-mannosylation plays an important role in various protein functions.
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| Academic Significance and Societal Importance of the Research Achievements |
ポストゲノム時代においてタンパク質の性質を理解することは重要である。特にヒトタンパク質は多くの翻訳後修飾を受けることで活性が制御されているため解析が困難である。本研究課題では、翻訳後修飾の中でも最も解析が遅れていた糖修飾に着目したものである。中でもC型糖修飾は報告されている基質タンパク質の数が少なく未解明な点が多いが、本研究により新たに4つの基質タンパク質を同定することができた。この中のいくつかは疾病に関連するものもあるため、当該研究分野に多大な貢献をすることができた。
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Report
(4 results)
Research Products
(61 results)
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[Journal Article] Gilteritinib overcomes lorlatinib resistance in ALK-rearranged cancer2021
Author(s)
Mizuta Hayato、Okada Koutaroh、Araki Mitsugu、Adachi Jun、Takemoto Ai、Kutkowska Justyna、Maruyama Kohei、Friboulet Luc、Katayama Kazuhiro、Ma Biao、Sasakura Yoko、Sagae Yukari、Kukimoto-Niino Mutsuko、Shirouzu Mikako、Takagi Satoshi、Simizu Siro、Nishio Makoto、Okuno Yasushi、Fujita Naoya、Katayama Ryohei, et al
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Journal Title
Nature Communications
Volume: 12
Pages: 1261-1261
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Unified total synthesis of madangamine alkaloids.2019
Author(s)
Suto, T., Yanagita, Y., Nagashima, Y., Takikawa, S., Kurosu, Y., Matsuo, N., Miura, K., Simizu, S., Sato, T. & Chida, N.
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Journal Title
Bulletin of the Chemical Society of Japan
Volume: 92
Pages: 545-571
NAID
Related Report
Peer Reviewed
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[Journal Article] C-mannosylation of R-spondin2 activates Wnt/β-catenin signaling and migration activity in human tumor cells.2019
Author(s)
Mizuta, H., Kuga, K., Suzuki, T., Niwa, Y., Dohmae, N. & Simizu, S.
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Journal Title
International Journal of Oncology
Volume: -
Pages: 2127-2138
DOI
Related Report
Peer Reviewed
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