2018 Fiscal Year Final Research Report
Peptidomics for studying limited proteolysis in pancreatic cancer
| Project/Area Number |
16K09404
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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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| Research Field |
Gastroenterology
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| Research Institution | Sasaki Foundation (2018)
National Cardiovascular Center Research Institute (2016-2017) |
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Principal Investigator |
Sasaki Kazuki 公益財団法人佐々木研究所, 附属研究所, 部長(移行) (80260313)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 膵腺癌 / ペプチド / 限定分解 / 質量分析 |
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| Outline of Final Research Achievements |
We used mass spectrometry-based profiling of endogenous peptides released in medium by cultured pancreatic cancer cell lines and immortalized pancreatic duct cell lines in order to identify specific, extracellular proteolytic processing sites of secretory or transmembrane proteins. Sequenced peptides were aligned on each parent precursor to generate proteolytic processing maps. Some known processing sites such as peptide hormone processing or transmembrane protein ectodomain shedding were recapitulated by this peptidomic profiling. In-depth analysis of endogenous peptides would highlight more transmembrane proteins regulated by ectodomain shedding. Accumulated profiling information can be used for identifying transmembrane proteins that could be a potential target for treating pancreatic cancer.
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| Free Research Field |
細胞生物学
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| Academic Significance and Societal Importance of the Research Achievements |
膜タンパク質のプロセシング部位を特定することは、新規生理活性ペプチドの生成部位の手がかりを提供するだけではなく、抗体医薬の設計に必要な基盤情報の提供にも役立つ。従来は部位の特定は、個別的な生化学・分子生物学的な研究で実施されてきた。しかし、本研究では、質量分析法の進歩で可能となったペプチドミクスの手法を活用することで、膜タンパク質のプロセシング部位をトランスフェクションなどを介することなく、そのままの形で特定できるようになったことが大きな進歩である。深達度の高い解析で、治療の標的となる分子の特定が期待される。
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