2020 Fiscal Year Final Research Report
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 |
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| 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) |
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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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| Keywords | 大腸腫瘍 / TNF |
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| 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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| Free Research Field |
下部消化管
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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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