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Elucidation of mechanisms of disease pathogenesis caused by ubiquitin ligase deficiency.

Research Project

Project/Area Number 25860241
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pathological medical chemistry
Research InstitutionKyushu University

Principal Investigator

KANAE Yumimoto  九州大学, 生体防御医学研究所, 研究員 (30596838)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsユビキチンリガーゼ / プロテオミクス / 骨分化制御 / 軟骨分化制御 / 時計制御
Outline of Final Research Achievements

We aim to reveal the mechanisms of pathogenesis by elucidating the relationship between a ubiquitin ligase and its substrates. We previously developed a new approach, termed DiPIUS (differential proteomics-based identification of ubiquitylation substrates), to discover substrates of ubiquitin ligases. We revealed that Fbxw7 controls osteoblast and chondrocyte differentiation by targeting OASIS and BBF2H7, basic leucine zipper (bZIP) type transcription factors, for proteasome-mediated degradation. We also showed that DEAD-box RNA helicase DDX24 is a substrate for MDM2.
We also showed that Fbxw7 inhibits cancer metastasis in non-cell autonomous manner by targeting Notch for degradation.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (11 results)

All 2015 2014 2013 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (3 results) Book (1 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] F-box protein FBXW7 inhibits cancer metastasis in a non-cell-autonomous manner2015

    • Author(s)
      Yumimoto, K., Akiyoshi, S., Ueo, H., Sagara, Y., Onoyama, I., Ueo, H., Ohno, S., Mori, M., Mimori, K., Nakayama, K. I.
    • Journal Title

      J. Clin. Invest.

      Volume: 125 Issue: 2 Pages: 621-635

    • DOI

      10.1172/jci78782

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of GATA binding protein 2 levels via ubiquitin-dependent degradation by Fbw7: involvement of cyclin B-cyclin-dependent kinase 1-mediated phosphorylation of Thr176 in GATA binding protein 2.2015

    • Author(s)
      Nakajima T, Kitagawa K, Ohhata T, Sakai S, Uchida C, Shibata K, Minegishi N, Yumimoto K, Nakayama K-I, Masumoto K, Katou F, Niida H, Kitagawa M
    • Journal Title

      J Biol Chem

      Volume: 290 Issue: 16 Pages: 10368-10381

    • DOI

      10.1074/jbc.m114.613018

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MDM2 mediates nonproteolytic polyubiquitylation of the DEAD-Box RNA helicase DDX242014

    • Author(s)
      Yamauchi, T., Nishiyama, M., Moroishi, T., Yumimoto, K., Nakayama, K. I.
    • Journal Title

      Molecular and Cellular Biology

      Volume: 34 Issue: 17 Pages: 3321-3340

    • DOI

      10.1128/mcb.00320-14

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] F-box and WD repeat domain containing-7 (Fbxw7) targets endoplasmic reticulum-anchored osteogenic and chondrogenic transcriptional factors for degradation2013

    • Author(s)
      Yumimoto K., Matsumoto M., Onoyama I., Imaizumi K., Nakayama KI.
    • Journal Title

      J. Biol. Chem.

      Volume: 288 Issue: 40 Pages: 28488-502

    • DOI

      10.1074/jbc.m113.465179

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Substrate binding promotes formation of the Skp1-Cul1-Fbxl3 (SCF(Fbxl3)) protein complex2013

    • Author(s)
      Yumimoto, K. Muneoka, T. Tsuboi, T. Nakayama, K. I.
    • Journal Title

      J. Biol. Chem.

      Volume: 288 Issue: 45 Pages: 32766-32776

    • DOI

      10.1074/jbc.m113.511303

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 癌周囲の微小環境におけるFbxw7の発現量が癌転移能を規定する2014

    • Author(s)
      3.弓本佳苗、秋吉清百合、上尾裕紀、小野山一郎、上尾裕昭、森正樹、三森功士、中山敬一
    • Organizer
      第37回日本分子生物学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Comprehensive identification of substrates for F-box proteins by differential proteomics analysis. , Jul.2013

    • Author(s)
      Kanae Yumimoto, Masaki Matsumoto, Koji Oyamada, Toshiro Moroishi, Keiichi I. Nakayama
    • Organizer
      The 35th Naito Conference
    • Place of Presentation
      ガトーキングダムサッポロ
    • Related Report
      2013 Research-status Report
  • [Presentation] Substrate binding promotes formation of the Skp1-Cul1-Fbxl3 (SCF/Fbxl3) complex.2013

    • Author(s)
      Kanae Yumimoto, Tetsuya Muneoka, Tomohiro Tsuboi, Keiichi I. Nakayama
    • Organizer
      The 37th Annual Meeting of the Molecular Biology Society of Japan
    • Place of Presentation
      神戸ポートアイランド
    • Related Report
      2013 Research-status Report
  • [Book] 実験医学2015

    • Author(s)
      弓本佳苗、中山敬一
    • Publisher
      羊土社
    • Related Report
      2014 Annual Research Report
  • [Remarks] 九州大学生体防御医学研究所分子医科学分野

    • URL

      http://www.bioreg.kyushu-u.ac.jp/saibou/index.html

    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] 有機酸重合体を有効成分とする癌細胞の生着予防又は生着抑制のための医薬2013

    • Inventor(s)
      中山 敬一
    • Industrial Property Rights Holder
      中山 敬一
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-08-06
    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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