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Molecular basis of angiogenesis regulated by CUL3-dependent membrane trafficking

Research Project

Project/Area Number 16K19038
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General medical chemistry
Research InstitutionEhime University

Principal Investigator

Maekawa Masashi  愛媛大学, プロテオサイエンスセンター, テニュアトラック助教 (10771917)

Research Collaborator HIGASHIYAMA Shigeki  愛媛大学, プロテオサイエンスセンター, 教授 (60202272)
SAKAUE Tomohisa  愛媛大学, 大学院・医学系研究科, 助教 (20709266)
TAGUCHI Tomohiko  東北大学, 大学院・生命科学研究科, 教授 (10300881)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords血管新生 / CUL3 / 細胞内膜輸送 / Integrin β1 / 血管内皮細胞 / ユビキチンE3リガーゼ
Outline of Final Research Achievements

Angiogenesis, the formation of new blood vessels, is related to not only development but a variety of diseases like tumor growth/metastasis. Anti-angiogenic drugs are successfully used for cancer therapy. In this study, we identified a novel angiogenic factor, the CUL3/ANKFY1 ubiquitin E3 ligase complex, which determines the cell surface level of integrin, an essential adhesion molecule for angiogenesis. CUL3/ANKFY1 regulated recycling of integrin from endosomes to the plasma membrane in human endothelial cells. The CUL3/ANKFY1 complex might be an attractive protein complex to develop novel anti-angiogenic drugs.

Report

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

    (14 results)

All 2018 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (8 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 8 results,  Open Access: 7 results,  Acknowledgement Compliant: 2 results) Presentation (3 results) Patent(Industrial Property Rights) (2 results)

  • [Int'l Joint Research] Sanquin Research/Vrije Universiteit University(オランダ)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] The Cullin-3-Rbx1-KCTD10 complex controls endothelial barrier function via K63 ubiquitination of RhoB2018

    • Author(s)
      Kovacevic Igor、Sakaue Tomohisa、Majolee Jisca、Pronk Manon C.、Maekawa Masashi、Geerts Dirk、Fernandez-Borja Mar、Higashiyama Shigeki、Hordijk Peter L.
    • Journal Title

      The Journal of Cell Biology

      Volume: 217 Issue: 3 Pages: 1015-1032

    • DOI

      10.1083/jcb.201606055

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cullin 3 regulates ADAMs-mediated ectodomain shedding of amphiregulin2018

    • Author(s)
      Nakayama Hironao、Sakaue Tomohisa、Maekawa Masashi、Fujisaki Ayako、Higashiyama Shigeki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 499 Issue: 1 Pages: 17-23

    • DOI

      10.1016/j.bbrc.2018.03.097

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cullin-3 and its adaptor protein ANKFY1 determine the surface level of integrin beta1 in endothelial cells.2017

    • Author(s)
      Maekawa M, Tanigawa K, Sakaue T, Hiyoshi H, Kubota E, Joh T, Watanabe Y, Taguchi T, Higashiyama S
    • Journal Title

      Biolology Open

      Volume: 6 Pages: 1707-1719

    • DOI

      10.1242/bio.029579

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prospect of divergent roles for the CUL3 system in vascular endothelial cell function and angiogenesis2017

    • Author(s)
      Sakaue Tomohisa、Maekawa Masashi、Nakayama Hironao、Higashiyama Shigeki
    • Journal Title

      The Journal of Biochemistry

      Volume: 162 Pages: 237-245

    • DOI

      10.1093/jb/mvx051

    • NAID

      40021380486

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neddylated Cullin 3 is required for vascular endothelial-cadherin-mediated endothelial barrier function.2017

    • Author(s)
      Sakaue T, Fujisaki A, Nakayama H, Maekawa M, Hiyoshi H, Kubota E, Joh T, Izutani H, Higashiyama S.
    • Journal Title

      Cancer Sci.

      Volume: 108 Issue: 2 Pages: 208-215

    • DOI

      10.1111/cas.13133

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Domain 4 (D4) of Perfringolysin O to Visualize Cholesterol in Cellular Membranes-The Update.2017

    • Author(s)
      Maekawa M
    • Journal Title

      Sensors (Basel)

      Volume: 17 Issue: 3 Pages: 504-504

    • DOI

      10.3390/s17030504

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Perfringolysin O Theta Toxin as a Tool to Monitor the Distribution and Inhomogeneity of Cholesterol in Cellular Membranes.2016

    • Author(s)
      Maekawa M, Yang Y, Fairn GD
    • Journal Title

      Toxins (Basel)

      Volume: 8 Issue: 3 Pages: 67-67

    • DOI

      10.3390/toxins8030067

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Staurosporines decrease ORMDL proteins and enhance sphingomyelin synthesis resulting in depletion of plasmalemmal phosphatidylserine.2016

    • Author(s)
      Maekawa M, Lee M, Wei K, Ridgway ND, Fairn GD
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 35762-35762

    • DOI

      10.1038/srep35762

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 低濃度staurosporine処理によるスフィンゴミエリンの生合成亢進を介したホスファチジルセリンの細胞膜局在制御2017

    • Author(s)
      前川大志
    • Organizer
      第58回 日本生化学会 中国・四国支部例会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 血管内皮細胞におけるユビキチンE3リガーゼ複合体依存的な細胞内膜輸送2017

    • Author(s)
      前川大志
    • Organizer
      ConBio2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] 生体膜の細胞質側のコレステロールを可視化する新規コレステロールプローブD4Hの開発と応用2016

    • Author(s)
      前川大志
    • Organizer
      第57回 日本生化学会 中国・四国支部例会
    • Place of Presentation
      高知大学
    • Year and Date
      2016-05-28
    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] 細胞内輸送を介した膜蛋白質の分解又はリサイクリングの制御剤2017

    • Inventor(s)
      東山繁樹、前川大志、坂上倫久、城卓志、久保田英嗣
    • Industrial Property Rights Holder
      東山繁樹、前川大志、坂上倫久、城卓志、久保田英嗣
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-244776
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 血管新生制御剤及びその利用法2017

    • Inventor(s)
      東山繁樹、前川大志、坂上倫久、城卓志、久保田英嗣
    • Industrial Property Rights Holder
      東山繁樹、前川大志、坂上倫久、城卓志、久保田英嗣
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-193118
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report

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Published: 2016-04-21   Modified: 2019-03-29  

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