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An attempt to develop novel CaM kinase phosphatase inhibitors that are effective for suppression of cancer metastasis with low cytotoxicity

Research Project

Project/Area Number 15K01824
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Chemical biology
Research InstitutionHiroshima University

Principal Investigator

Ishida Atsuhiko  広島大学, 総合科学研究科, 教授 (90212886)

Co-Investigator(Kenkyū-buntansha) 根平 達夫  広島大学, 総合科学研究科, 准教授 (60321692)
石原 康宏  広島大学, 総合科学研究科, 助教 (80435073)
Research Collaborator HIDE Michihiro  広島大学, 大学院・医歯薬保健学研究科, 教授 (50284188)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsプロテインホスファターゼ / 阻害剤 / スクリーニング / がん転移・浸潤 / 細胞遊走 / 細胞毒性 / 構造機能相関 / 特異的阻害剤 / 乳がん細胞 / 遊走 / 膜透過性 / ホスファターゼ / タンパク質カルボニル化 / 反応機構 / 特異性 / 活性化因子 / プロトカドヘリン / 浸潤
Outline of Final Research Achievements

CaM kinase phosphatase (CaMKP/PPM1F/POPX2) is a Ser/Thr protein phosphatase that belongs to PPM family. Accumulating evidence shows possible involvement of CaMKP in cancer metastasis. In this study, we carried out large-scale screening of chemical library to find CaMKP-specific inhibitors, and investigated a mechanism of action of the inhibition. Subsequently, we showed that some of these inhibitors effectively suppressed migration of breast cancer cells despite the fact that they had no significant toxic effects on the cells. These data suggest that these CaMKP inhibitors or the derivatives are promising lead compounds for the development of novel cancer metastasis inhibitors without significant cytotoxicity.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (19 results)

All 2018 2017 2016 2015 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Int'l Joint Research: 1 results) Book (1 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Functions and dysfunctions of Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP/PPM1F) and CaMKP-N/PPM1E2018

    • Author(s)
      Ishida A, Sueyoshi N, Kameshita I
    • Journal Title

      Arch Biochem Biophys.

      Volume: 640 Pages: 83-92

    • DOI

      10.1016/j.abb.2018.01.001

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Facile preparation of highly active casein kinase 1 using Escherichia coli constitutively expressing lambda phosphatase2018

    • Author(s)
      Akizuki Kazutoshi、Toyama Taku、Yamashita Masashi、Sugiyama Yasunori、Ishida Atsuhiko、Kameshita Isamu、Sueyoshi Noriyuki
    • Journal Title

      Analytical Biochemistry

      Volume: 549 Pages: 99-106

    • DOI

      10.1016/j.ab.2018.03.015

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of CoPK02, a Ca2+/calmodulin-dependent protein kinase in mushroom Coprinopsis cinerea.2018

    • Author(s)
      Yamashita M, Sueyoshi N, Yamada H, Katayama S, Senga Y, Takenaka Y, Ishida A, Kameshita I, Shigeri Y
    • Journal Title

      Biosci Biotechnol Biochem.

      Volume: in press Issue: 8 Pages: 1335-1343

    • DOI

      10.1080/09168451.2018.1462692

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP/PPM1F) interacts with neurofilament L and inhibits its filament association.2016

    • Author(s)
      Ozaki H, Katoh T, Nakagawa R, Ishihara Y, Sueyoshi N, Kameshita I, Taniguchi T, Hirano T, Yamazaki T, Ishida A
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 477 Issue: 4 Pages: 820-825

    • DOI

      10.1016/j.bbrc.2016.06.141

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] High-performance CaMKI: A highly active and stable form of CaMKIδ produced by high-level soluble expression in Escherichia coli.2016

    • Author(s)
      Senga Y, Akizuki K, Katayama S, Shigeri Y, Kameshita I, Ishida A, Sueyoshi N
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 475 Issue: 3 Pages: 277-282

    • DOI

      10.1016/j.bbrc.2016.05.060

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] The phosphatase-resistant isoform of CaMKI, Ca2+/calmodulin-dependent protein kinase Iδ (CaMKIδ), remains in its 'Primed' form without Ca2+-stimulation.2015

    • Author(s)
      Senga Y, Ishida A, Shigeri Y, Kameshita I, Sueyoshi N.
    • Journal Title

      Biochemistry

      Volume: 54 Issue: 23 Pages: 3617-3630

    • DOI

      10.1021/bi5012139

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regulation of Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP/PPM1F) by protocadherin-gamma C5 (Pcdh-gamma C5)2015

    • Author(s)
      Onouchi T, Kishino-Kaneko Y, Kameshita I, Ishida A, Sueyoshi N.
    • Journal Title

      Arch Biochem Biophys

      Volume: 585 Pages: 109-120

    • DOI

      10.1016/j.abb.2015.09.014

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 非リン酸化型プロテインキナーゼの簡易調製法の開発とそれを活用した高活性型CK1 の取得2017

    • Author(s)
      秋月一駿, 山下雅史, 遠山拓, 石田敦彦, 亀下勇, 末吉紀行
    • Organizer
      日本電気泳動学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] λ phosphataseを恒常的に発現する大腸菌株BL21(DE3)pλPPを利用した 高活性型casein kinase 1の簡便な調製法2017

    • Author(s)
      秋月 一駿、遠山 拓、石田 敦彦、亀下 勇、末吉 紀行
    • Organizer
      ConBio2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] Interleukin-1αの線維芽細胞における細胞内局在制御機構2017

    • Author(s)
      早弓 恵里香、田内 香帆、林 亜里香、山﨑 岳、石田 敦彦、平野 哲男
    • Organizer
      ConBio2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP/PPM1F) interacts with neurofilament L and inhibits its filament association2016

    • Author(s)
      Hana Ozaki, Tsuyoshi Katoh, Ryoko Nakagawa, Yasuhiro Ishihara, Noriyuki Sueyoshi, Isamu Kameshita, Takanobu Taniguchi, Tetsuo Hirano, Takeshi Yamazaki, Atsuhiko Ishida
    • Organizer
      第12回プロテインホスファターゼ国際カンファレンス
    • Place of Presentation
      東大阪市・近畿大学
    • Year and Date
      2016-10-27
    • Related Report
      2016 Research-status Report
  • [Presentation] Protein conformational analysis by fluorescence-detected circular dichroism (FDCD)2015

    • Author(s)
      Tatsuo Nehira, Kaoru Ishihara, Hirone Ito, Keiko Masuda, Kazuyoshi Ukena, Koichi Matsuo, Shunsuke Izumi, Takeshi Yamazaki, and Atsuhiko Ishida
    • Organizer
      The International Chemical Congress of Pacific Basin Societies 2015
    • Place of Presentation
      Honolulu, Hawaii, USA
    • Year and Date
      2015-12-14
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] CaMキナーゼホスファターゼはニューロフィラメント Lと結合して重合を阻害する2015

    • Author(s)
      尾崎 華 , 加藤 剛志 , 中川 綾.子 , .石原 康宏 , 末吉 紀.行. , .亀下 勇 , .谷.口 隆信 , .山崎 岳 , .石.田 敦彦
    • Organizer
      第38回日本分子生物学会年会・第88回日本生化学会大会合同大会
    • Place of Presentation
      松江市
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] 蛍光検出円二色性(FDCD)分光法が可能にする タンパク質立体構造変化の検出2015

    • Author(s)
      伊藤弘音、根平達夫、石原郁、益田恵子、浮穴和義、松尾光一、泉俊輔、山﨑岳、石田敦彦
    • Organizer
      第56回日本生化学会中国・四国支部例会
    • Place of Presentation
      神戸市
    • Year and Date
      2015-05-29
    • Related Report
      2015 Research-status Report
  • [Book] 材料表面の親水・親油の評価と制御設計(石井淑夫監修)2016

    • Author(s)
      石田敦彦、亀下勇(「インゲルキナーゼ・ホスファターゼアッセイ法」の項の分担執筆)
    • Total Pages
      600
    • Publisher
      テクノシステム (東京)
    • Related Report
      2016 Research-status Report
  • [Remarks] 広島大学大学院総合科学研究科分子脳科学研究室

    • URL

      http://home.hiroshima-u.ac.jp/ishiyasu/

    • Related Report
      2017 Annual Research Report 2015 Research-status Report
  • [Remarks] 広島大学大学院総合科学研究科 分子脳科学研究室

    • URL

      http://home.hiroshima-u.ac.jp/ishiyasu/index.html

    • Related Report
      2016 Research-status Report
  • [Remarks] 広島大学研究者総覧

    • URL

      http://seeds.office.hiroshima-u.ac.jp/profile/ja.2ee080ff39c4e712520e17560c007669.html

    • Related Report
      2015 Research-status Report
  • [Patent(Industrial Property Rights)] カルモジュリン依存性タンパク質リン酸化酵素Ⅰ由来ポリペプチド、リン酸化剤、および製造方法2016

    • Inventor(s)
      千賀、茂里、秋月、片山、末吉、亀下、石田
    • Industrial Property Rights Holder
      産業技術総合研究所、香川大学、広島大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-095770
    • Filing Date
      2016-05-12
    • Related Report
      2016 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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