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Peptidomics for studying limited proteolysis in pancreatic cancer

Research Project

Project/Area Number 16K09404
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionSasaki Foundation (2018)
National Cardiovascular Center Research Institute (2016-2017)

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)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords膵腺癌 / ペプチド / 限定分解 / 質量分析 / タンパク質切断 / ペプチドミクス / 膵臓学
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.

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。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (7 results)

All 2018 2017 2016 Other

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (1 results) (of which Int'l Joint Research: 1 results) Remarks (1 results)

  • [Journal Article] Isolation of Endogenous Peptides from Cultured Cell Conditioned Media for Mass Spectrometry2018

    • Author(s)
      Sasaki Kazuki、Tsuchiya Takashi、Osaki Tsukasa
    • Journal Title

      Methods in Molecular Biology

      Volume: 1719 Pages: 51-58

    • DOI

      10.1007/978-1-4939-7537-2_3

    • ISBN
      9781493975365, 9781493975372
    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Endogenous peptide profile for elucidating biosynthetic processing of the ghrelin precursor2017

    • Author(s)
      Tsuchiya Takashi、Iwakura Hiroshi、Minamino Naoto、Kangawa Kenji、Sasaki Kazuki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 490 Issue: 4 Pages: 1142-1146

    • DOI

      10.1016/j.bbrc.2017.06.155

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] ペプチドミクスを活用した生理活性ペプチドの発見2017

    • Author(s)
      佐々木一樹
    • Journal Title

      生化学

      Volume: 89 Pages: 894898-894898

    • NAID

      40021439312

    • Related Report
      2017 Research-status Report
  • [Journal Article] NERP-2 regulates gastric acid secretion and gastric emptying via the orexin pathway.2017

    • Author(s)
      Cherl Namkoong, Koji Toshinai, Zaved Waise, Hideyuki Sakoda, Kazuki Sasaki, Yoichi Ueta, Min-Seon Kim, Naoto Minamino, Masamitsu Nakazato.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 485 Issue: 2 Pages: 409-413

    • DOI

      10.1016/j.bbrc.2017.02.064

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Characterization of gonadotrope secretoproteome identifies neurosecretory protein VGF-derived peptide suppression of follicle-stimulating hormone gene expression2016

    • Author(s)
      Choi SG, Wang Q, Jia J, Chikina M, Pincas H, Dolios G, Sasaki K, Wang R, Minamino N, Salton SR, Sealfon SC
    • Journal Title

      Journal of Biological Chemistry

      Volume: 291 Pages: 2132221334-2132221334

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Endogenous Peptide Profiling for Studying Limited Proteolysis2017

    • Author(s)
      Kazuki Sasaki
    • Organizer
      PepCon2017
    • Place of Presentation
      福岡
    • Year and Date
      2017-03-23
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] 公益財団法人佐々木研究所附属佐々木研究所ペプチドミクス研究部

    • URL

      http://www.sasaki-institute.org/peptidomics/

    • Related Report
      2018 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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