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Highly sensitive detection of ubiquitination using tumor-bearing mouse model

Research Project

Project/Area Number 26430147
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor diagnostics
Research InstitutionHimeji Dokkyo University

Principal Investigator

Miyamoto Kazuhide  姫路獨協大学, 薬学部, 准教授 (10415317)

Co-Investigator(Kenkyū-buntansha) 炬口 真理子  姫路獨協大学, 薬学部, 准教授 (10379430)
谷口 泰造  姫路獨協大学, 薬学部, 教授 (70346253)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsユビキチン化 / がん診断 / ユビキチンリガーゼ / E2活性 / ARF / がん / 診断 / ユビキチン / バイオマーカー / 癌診断
Outline of Final Research Achievements

The ubiquitin-conjugating enzymes (E2) in ubiquitination are associated with various diseases such as leukemia, lung cancer, and breast cancer. Thus, assessing E2 activity leads to the monitoring of tumor development for diagnostic and prognostic purposes. Here, we described the detection of E2 activity on a signal accumulation ISFET biosensor (AMIS sensor) using an artificial RING finger (ARF). The use of ARF enabled the simplified detection of E2 activity without a substrate. The high-sensitivity quantitative detection of E2 activities was demonstrated via real-time monitoring over a response range of femtomolar to micromolar concentrations. Furthermore, the monitoring of E2 activities was successfully achieved using human acute promyelocytic leukemia cells following treatment with the anticancer drug bortezomib, which allowed the assessment of the pathological conditions.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (29 results)

All 2017 2016 2015 2014 Other

All Journal Article (6 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 6 results,  Acknowledgement Compliant: 4 results,  Open Access: 1 results) Presentation (20 results) (of which Invited: 3 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] 人工ユビキチンリガーゼの分子設計法の開発とその応用2017

    • Author(s)
      宮本和英,砂川真弓, 齋藤一樹
    • Journal Title

      分析化学(総合論文)

      Volume: -

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Highly sensitive detection of E2 activity in ubiquitination using an artificial RING finger2017

    • Author(s)
      Miyamoto K, Sumida M, Yuasa-Sunagawa M, Saito K
    • Journal Title

      J Pept Sci.

      Volume: 23 Issue: 3 Pages: 222-227

    • DOI

      10.1002/psc.2972

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Rapid and accurate monitoring of E2 activities using an artificial E3 ligase on a signal accumulation ISFET biosensor2016

    • Author(s)
      Miyamoto K, Sumida M, Sunagawa M
    • Journal Title

      Peptide Science

      Volume: - Pages: 171-172

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The Artifical Ubiquitin Ligase E3 Inhibits Cellular Proliferation in Cancer Cells2016

    • Author(s)
      Sunagawa M, Nakatani A, Miyamoto K
    • Journal Title

      Peptide Science

      Volume: - Pages: 125-126

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Improved isolation procedure for shikonin from the root of the Chinese medicinal plant Lithospermum erythrorhizon and its solubilization with cyclodextrins2016

    • Author(s)
      Hideki Azuma, Jiawei Li, Ryota Youda, Toshio Suzuki, Kazuhide Miyamoto, Taizo Taniguchi, Takeshi Nagasaki
    • Journal Title

      J. Appl. Res. Med. Arom Plants

      Volume: 3 Issue: 2 Pages: 58-63

    • DOI

      10.1016/j.jarmap.2016.01.002

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Structural model of ubiquitin transfer onto an artificial RING finger as an E3 ligase2014

    • Author(s)
      Kazuhide Miyamoto
    • Journal Title

      Scientific Reports

      Volume: 4 Issue: 1 Pages: 6574-6574

    • DOI

      10.1038/srep06574

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] ユビキチン化反応におけるE2活性のリアルタイム検出法2017

    • Author(s)
      宮本
    • Organizer
      超異分野学会 大阪フォーラム2017
    • Place of Presentation
      立命館大学
    • Year and Date
      2017-03-11
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Real-time detection of E2 activities in the ubiquitination reaction using an artificial E3 ligase2016

    • Author(s)
      宮本、澄田、砂川
    • Organizer
      第39回日本分子生物学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Creation of an artificial E3 ligase and its anticancer effects2016

    • Author(s)
      宮本、砂川、中谷
    • Organizer
      第39回日本分子生物学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] 人工ユビキチンリガーゼの分子設計法の構築2016

    • Author(s)
      宮本和英
    • Organizer
      第33回関西ペプチドセミナー
    • Place of Presentation
      近畿大学
    • Year and Date
      2016-11-26
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 人工ユビキチンリガーゼによる急性前骨髄性白血病の抑制効果2016

    • Author(s)
      宮本、中谷、砂川、齋藤、
    • Organizer
      第33回関西ペプチドセミナー
    • Place of Presentation
      近畿大学
    • Year and Date
      2016-11-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] Rapid and accurate monitoring of E2 activities using an artificial E3 ligase on a signal accumulation ISFET biosensor2016

    • Author(s)
      宮本、澄田、砂川
    • Organizer
      第53回ペプチド討論会
    • Place of Presentation
      京都テルサ
    • Year and Date
      2016-10-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] The artificial ubiquitin ligase E3 inhibits cellular proliferation in cancer cells2016

    • Author(s)
      宮本、砂川、中谷
    • Organizer
      第53回ペプチド討論会
    • Place of Presentation
      京都テルサ
    • Year and Date
      2016-10-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] 新規抗がん剤としての人工ユビキチンリガーゼの設計とその作用機序2016

    • Author(s)
      宮本、砂川、齋藤
    • Organizer
      第66回日本薬学会近畿支部
    • Place of Presentation
      大阪薬科大学
    • Year and Date
      2016-10-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] ユビキチン結合酵素(E2)活性の検出に基づく腫瘍サイズの決定2016

    • Author(s)
      宮本、砂川、齋藤
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] 人工ユビキチンリガーゼを用いるユビキチン結合酵素(E2)活性の検出法2016

    • Author(s)
      宮本、砂川、齋藤
    • Organizer
      第65回日本分析化学会
    • Place of Presentation
      北海道大学
    • Year and Date
      2016-09-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] 人工ユビキチンリガーゼを用いた血清中のユビキチン化反応の検出法2016

    • Author(s)
      宮本、砂川、齋藤
    • Organizer
      第29回バイオメディカル分析科学シンポジウム
    • Place of Presentation
      京都大学
    • Year and Date
      2016-09-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] 人工ユビキチンリガーゼのがん細胞増殖抑制効果2016

    • Author(s)
      宮本、中谷、砂川、齋藤
    • Organizer
      第29回バイオメディカル分析科学シンポジウム
    • Place of Presentation
      京都大学
    • Year and Date
      2016-09-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] 癌などの重篤疾患の治療前診断法2016

    • Author(s)
      宮本
    • Organizer
      企業・大学・学生マッチング
    • Place of Presentation
      兵庫県立大
    • Year and Date
      2016-05-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] Structural analysis of ubiquitin transfer onto an artificial E3 ligase2015

    • Author(s)
      宮本和英
    • Organizer
      第38回日本分子生物学会
    • Place of Presentation
      神戸国際会議場(神戸市)
    • Year and Date
      2015-12-02
    • Related Report
      2015 Research-status Report
  • [Presentation] 癌などの重篤疾患の治療前診断法2015

    • Author(s)
      宮本和英
    • Organizer
      国際フロンティア産業メッセ
    • Place of Presentation
      神戸国際会議場(神戸市)
    • Year and Date
      2015-09-04
    • Related Report
      2015 Research-status Report
  • [Presentation] 癌などの重篤疾患の治療前診断法2015

    • Author(s)
      宮本和英
    • Organizer
      企業・大学・学生マッチング
    • Place of Presentation
      兵庫県立大(姫路市)
    • Year and Date
      2015-05-28
    • Related Report
      2015 Research-status Report
  • [Presentation] ユビキチンプロテアソームと疾患診断法2015

    • Author(s)
      宮本和英
    • Organizer
      メディカルジャパン2015
    • Place of Presentation
      インテックス大阪(大阪)
    • Year and Date
      2015-02-06
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Ubiquitination on an artificial RING finger as an E3 ligase2014

    • Author(s)
      宮本和英
    • Organizer
      第51回ペプチド討論会
    • Place of Presentation
      徳島大(徳島)
    • Year and Date
      2014-10-22
    • Related Report
      2014 Research-status Report
  • [Presentation] ユビキチン化を用いた新しい診断法2014

    • Author(s)
      宮本和英
    • Organizer
      国際フロンティア産業メッセ
    • Place of Presentation
      神戸国際展示場(神戸)
    • Year and Date
      2014-09-14
    • Related Report
      2014 Research-status Report
  • [Presentation] ユビキチン化を用いた新しい診断法2014

    • Author(s)
      宮本和英
    • Organizer
      企業・大学・学生マッチング
    • Place of Presentation
      兵庫県立大(姫路)
    • Year and Date
      2014-05-29
    • Related Report
      2014 Research-status Report
  • [Remarks] 姫路獨協大学薬学部生物分析化学研究室HP

    • URL

      http://www.himeji-du.ac.jp/faculty/dp_pharm/pharm/bioanalysis/

    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] 人工合成疑似E3を有効成分とする、癌診断薬、抗癌剤選択支援剤、および天然E3に拮抗する阻害剤2015

    • Inventor(s)
      宮本和英,(株)行医研
    • Industrial Property Rights Holder
      宮本和英,(株)行医研
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-08-05
    • Acquisition Date
      2016-08-19
    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] キメラタンパク質(E2との選択的結合活性を有し標的タンパク質の必要なしにタンパク質のユビキチン化活性を示すタンパク質の提供)2015

    • Inventor(s)
      宮本和英,(株)行医研
    • Industrial Property Rights Holder
      宮本和英,(株)行医研
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-03-02
    • Acquisition Date
      2016-07-22
    • Related Report
      2016 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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