Comprehensive analysis of protein ubiquitination during a development of infection-induced cancer.
Project/Area Number |
17K19675
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Research Field |
Organ-based internal medicine and related fields
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Research Institution | Fukushima Medical University (2019-2020) Tokyo Medical and Dental University (2017-2018) |
Principal Investigator |
Onizawa Michio 福島県立医科大学, 医学部, 助教 (30783352)
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Co-Investigator(Kenkyū-buntansha) |
渡辺 守 東京医科歯科大学, 高等研究院, 特別栄誉教授 (10175127)
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Project Period (FY) |
2017-06-30 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Keywords | 大腸腫瘍 / TNF / サイトカイン / タンパク / 大腸癌 |
Outline of Final Research Achievements |
In this study using mouse models, we detected changes in the expression of various ubiquitinated proteins between non-tumor colitic epithelia and colitis-associated tumor tissue induced by administration of azoxymethane followed by sequential dextran sodium sulfate ingestion. The data obtained from these experiments are critical for understanding the physiology of colitis-associated tumor. We previously reported that the expression of TNFR2 is up-regulated in the tumor. However, the mechanism of TNFR2-mediated signal transduction is still poorly understood. We observed that Ikarugamycin increases the expression of the membrane form of TNF. This observation contributes to a better understanding of the TNF-TNFR2 pathway. In addition, our study indicates that there is a cellular mechanism by which the expression of TNF is terminated at the cellular level.
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Academic Significance and Societal Importance of the Research Achievements |
網羅的ユビキチン化修飾タンパク同定法は腫瘍発症機序解明やその予防法・治療法開発の基盤技術になりうると考える。また、細胞レベルでTNFの発現制御機構が存在しその破綻によりTNF産生が亢進するという概念は、炎症性発癌のみならず自己免疫性・炎症性疾患の病態解明に新たな視点を提供するものである。現在までTNF研究では、TNFR1に比べてTNFR2シグナルに関する知見が乏しかったが、本研究で明らかになった膜型TNFの効率的な誘導法は、膜型TNFを主なリガンドとするTNFR2に関する研究へ大きく貢献すると思われる。
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Report
(5 results)
Research Products
(47 results)
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[Journal Article] Intraepithelial Lymphocytes Suppress Intestinal Tumor Growth by Cell-to-Cell Contact via CD103/E-Cadherin Signal.2021
Author(s)
Ryo Morikawa, Yasuhiro Nemoto, Yuki Yonemoto, Shohei Tanaka, Yuria Takei, Shigeru Oshima, Takashi Nagaishi, Kiichiro Tsuchiya, Kengo Nozaki , Tomohiro Mizutani, Tetsuya Nakamura, Mamoru Watanabe, Ryuichi Okamoto.
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Journal Title
Cell Mol Gastroenterol Hepatol.
Volume: 11
Issue: 5
Pages: 1483-1503
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Nickel ions attenuate autophagy flux and induce transglutaminase 2 (TG2) mediated post-translational modification of SQSTM1/p62.2020
Author(s)
Emi Aonuma, Akiko Tamura, Hiroki Matsuda, Takehito Asakawa, Yuriko Sakamaki, Kana Otsubo, Yoichi Nibe, Michio Onizawa, Yasuhiro Nemoto, Takashi Nagaishi, Kiichiro Tsuchiya, Tetsuya Nakamura, Motohiro Uo, Mamoru Watanabe, Ryuichi Okamoto, Shigeru Oshima.
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Journal Title
Biochem Biophys Res Commun.
Volume: 542
Pages: 17-23
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] CEACAM1 specifically suppresses B cell receptor signaling-mediated activation..2020
Author(s)
Naoya Tsugawa, Daiki Yamada, Taro Watabe, Michio Onizawa, Shuang Wang, Yasuhiro Nemoto, Shigeru Oshima, Takeshi Tsubata, Takahiro Adachi, Yohei Kawano, Mamoru Watanabe, Richard S. Blumberg, Ryuichi Okamoto, Takashi Nagaishi.
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Journal Title
Biochem Biophys Res Commun.
Volume: 535
Pages: 99-105
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Receptor-Interacting Protein Kinase 3 (RIPK3) inhibits autophagic flux during necroptosis in intestinal epithelial cells.2020
Author(s)
Otsubo K, Maeyashiki C, Nibe Y, Tamura A, Aonuma E, Matsuda H, Kobayashi M, Onizawa M, Nemoto Y, Nagaishi T, Okamoto R, Tsuchiya K, Nakamura T, Torii S, Itakura E, Watanabe M, Oshima S.
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Journal Title
FEBS letters
Volume: 594
Issue: 10
Pages: 1586-1595
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] B cell activation in the cecal patches during the development of an experimental colitis model.2018
Author(s)
Taro Watabe, Takashi Nagaishi, Naoya Tsugawa, Yudai Kojima, Nisha Jose, Akinori Hosoya, Michio Onizawa, Yasuhiro Nemoto, Shigeru Oshima, Tetsuya Nakamura, Hajime Karasuyama, Takahiro Adachi, Mamoru Watanabe
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Journal Title
Biochem Biophys Res Commun.
Volume: 496
Issue: 2
Pages: 367-373
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Novel polyubiquitin imaging system, PolyUb-FC, reveals that K33-linked polyubiquitin is recruited by p62/SQSTM1.2017
Author(s)
Yoichi Nibe, Shigeru Oshima, Masanori Kobayashi, Chiaki Maeyashiki, Yu Matsuzawa, Kana Otsubo, Hiroki Matsuda, Emi Aonuma, Yasuhiro Nemoto, Takashi Nagaishi, Ryuichi Okamoto, Kiichiro Tsuchiya, Tetsuya Nakamura, Shinichiro Nakada, Mamoru Watanabe
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Journal Title
Autophagy.
Volume: 22
Issue: 2
Pages: 1-43
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] UC-related and segment-specific properties of patientderived colonic organoids.2019
Author(s)
Suzuki K, Shimizu H, Kawai M, Takahashi J, Anzai S, Kawamoto A, Nagata S, Hiraguri Y, Yui S, Tsuchiya K, Nakamura T, Ohtsuka K, Okamoto R, Watanabe M
Organizer
ECCO 2019
Related Report
Int'l Joint Research
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[Presentation] Synergy of Notch signalling and TNF-α in the inflamed intestinal epithelia of IBD patients leads to up-regulation of UBD, a ubiquitin-like protein.2019
Author(s)
Kawamoto A, Nagata S, Anzai S, Takahashi J, Kawai M, Hama M, Nogawa D, Yamamoto K, Kuno R, Suzuki K, Shimizu H, Hiraguri Y, Yui S, Oshima S, Tsuchiya K, Nakamura T, Ohtsuka K, Kitagawa M, Okamoto R, Watanabe M
Organizer
ECCO 2019
Related Report
Int'l Joint Research
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[Presentation] Single-cell level analysis of organoids derived from CD patients reveals disease-status related modifications of small intestinal stem cells.2018
Author(s)
Suzuki K, Kuwabara K, Takahashi J, Anzai S, Kuno R, Kawamoto A, Ishibashi F, Nagata S, Hiraguri Y, Yui S, Tsuchiya K, Nakamura T, Ohtsuka K, Okamoto R, Watanabe M
Organizer
DDW 2018
Related Report
Int'l Joint Research
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[Presentation] Mouse colonic secretory cells de-differentiate into intestinal stem cells and promote mucosal repair through activation of NF-KB signaling.2018
Author(s)
Ishibashi F, Shimizu H, Kawamoto A, Suzuki K, Anzai S, Kuwabara K, Takahashi J, Nagata S, Oshima S, Tsuchiya K, Nakamura T, Watanabe M, Okamoto R
Organizer
ISSCR 2018
Related Report
Int'l Joint Research
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[Presentation] Crohn’s disease patient-derived small intestinal organoids reveal disease-status related modification of stem cell properties2018
Author(s)
Suzuki K, Murano T, Hiraguri Y, Takahashi J, Shimizu H,Anzai S, Kuwabara K, Kawamoto A, Ishibashi F, Yui S, Tsuchiya K, Nakamura T, Ohtsuka K, Watanabe M, Okamoto R
Organizer
5th TERMIS World Congress 2018
Related Report
Int'l Joint Research
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[Presentation] Ectopic expression of reg3a in the mice distal Colon is mediated by interactions between notch and Il-22 signaling pathways, and promotes tissue repair By the augmentation of EGFR signaling.2018
Author(s)
Ishibashi F, Kuwabara K, Kawamoto A, Anzai S, Takahashi J, Nagata S, Shimizu H, Yui S, Oshima S, Tsuchiya K, Nakamura T, Watanabe M, Okamoto R
Organizer
UEGW 2018
Related Report
Int'l Joint Research
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[Presentation] Long-lived secretory cells residing in the mouse proximal colon serve as reserve stem cells under DNA damage-induced mucosal injury.2018
Author(s)
Kuwabara K, Ishibashi F, Kawamoto A, Anzai S, Takahashi J, Nagata S, Shimizu H, Yui S, Oshima S, Tsuchiya K, Nakamura T, Watanabe M, Okamoto R
Organizer
UEGW 2018
Related Report
Int'l Joint Research
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