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Cell signaling fine-tuning that supports animal tissue development and homeostasis

Research Project

Project/Area Number 25293072
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field General medical chemistry
Research InstitutionKyushu University

Principal Investigator

Tohru Ishitani  九州大学, 生体防御医学研究所, 准教授 (40448428)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywordsシグナルファインチューニング / 臓器構築 / NLK
Outline of Final Research Achievements

Animal tissues contain a variety of specialized cells and exert complex and accurate functions. Construction and maintenance of animal tissues are regulated by cell signaling pathways, such as Wnt and Shh signaling pathways. Interestingly, the number of cell signaling pathways is very few. Simple ON/OFF regulation of these few signaling pathways must be NOT sufficient to achieve the highly complex processes during tissue construction and maintenance. We believe that the spatial-temporal regulation of signaling pathways (Signal Fine-tuning) varies the roles of signaling pathways and contributes to tissue construction and maintenance. In this study, we focused on nemo-like kinase (NLK), which is a fine-tuner of Wnt signaling. We first revealed the molecular basis by which dysregulation of NLK causes malignant brain tumor. We also developed the small molecules that specifically inhibit NLK activity. We also discovered new molecules that fine-tune the activity of Wnt and Shh signaling.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (22 results)

All 2016 2015 2014 Other

All Int'l Joint Research (2 results) Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (16 results) (of which Int'l Joint Research: 1 results,  Invited: 5 results) Book (1 results) Remarks (1 results)

  • [Int'l Joint Research] Cleveland Clinic/Harvard Medical school(米国)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] University of Seoul/サムスンバイオメディカル研究所/成均館大学校(韓国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] In vivo RNAi screen identifies NLK as a negative regulator of mesenchymal activity in glioblastoma.2015

    • Author(s)
      Sa JK, Yoon Y, Kim M, Kim Y, Cho HJ, Lee JK, Kim GS, Han S, Kim WJ, Shin YJ, Joo KM, Paddison PJ, Ishitani T, *Lee J, *Nam DH.
    • Journal Title

      Oncotarget

      Volume: 6 Issue: 24 Pages: 20145-20159

    • DOI

      10.18632/oncotarget.3980

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hipk2 and PP1c cooperate to maintain Dvl protein levels required for Wnt signal transduction.2014

    • Author(s)
      Shimizu N, Ishitani S, Sato A, Shibuya H, Ishitani T.
    • Journal Title

      Cell Reports

      Volume: 8 Issue: 5 Pages: 1391-1404

    • DOI

      10.1016/j.celrep.2014.07.040

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Molecular systems that control Wnt/β-catenin signaling during animal tissue development and homeostasis.2016

    • Author(s)
      Tohru Ishitani
    • Organizer
      Seminar
    • Place of Presentation
      Universiti of Malaya, Kuala Lumpur, Malaysia
    • Year and Date
      2016-03-25
    • Related Report
      2015 Annual Research Report
  • [Presentation] Molecular systems that control Wnt/β-catenin signaling during animal tissue development and homeostasis.2016

    • Author(s)
      Tohru Ishitani
    • Organizer
      Seminar
    • Place of Presentation
      Universiti Putra Malaysia, Selangor, Malaysia
    • Year and Date
      2016-03-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] Ubiquitin-mediated NF-κB degradation directs dorsal-ventral patterning in vertebrate early embryo.2016

    • Author(s)
      Tohru Ishitani, Satoshi Anai, Shizuka Ishitani, Satoshi Ota
    • Organizer
      Keystone Symposia Ubiquitin Signaling
    • Place of Presentation
      Whistler Conference Centre, Whistler, Canada
    • Year and Date
      2016-03-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 動物組織構築を支えるシグナル制御機構の理解を目指して2016

    • Author(s)
      石谷 太
    • Organizer
      大阪大学微研セミナー
    • Place of Presentation
      大阪大学微生物学研究所
    • Year and Date
      2016-03-04
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 動物組織の構築・維持を支えるWnt/β-cateninシグナル制御機構2015

    • Author(s)
      石谷 太
    • Organizer
      難治疾患共同研究拠点シンポジウム
    • Place of Presentation
      東京医科歯科大学
    • Year and Date
      2015-11-26
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Spatially restricted Rel/NF-κB activation directs dorsal-ventral patterning in zebrafish2015

    • Author(s)
      Satoshi Anai, Satoshi Ota , Shizuka Ishitani, Tohru Ishitani
    • Organizer
      第21回 小型魚類研究会
    • Place of Presentation
      大阪大学銀杏会館
    • Year and Date
      2015-09-19
    • Related Report
      2015 Annual Research Report
  • [Presentation] タンパク質リン酸化酵素NLKはShhシグナルの負の制御を介して後脳組織の構築を支える2015

    • Author(s)
      Shizuka Ishitani, Nobuyuki Shimizu, Yusuke Takenoshita, Tohru Ishitani
    • Organizer
      第67回日本細胞生物学会大会
    • Place of Presentation
      タワーホール船堀
    • Year and Date
      2015-07-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] The NFκB transcription factor Rel fine-tunes dorsal-ventral pattern of zebrafish early embryos.2015

    • Author(s)
      Satoshi Anai, Satoshi Ota, Shizuka Ishitani, Tohru Ishitani
    • Organizer
      第48回日本発生生物学会
    • Place of Presentation
      つくば国際会議場
    • Year and Date
      2015-06-03
    • Related Report
      2015 Annual Research Report
  • [Presentation] 細胞運命を制御するタンパク質リン酸化酵素の活性制御化合物の探索2015

    • Author(s)
      石谷 閑, 山下智大, 石谷 太
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸学院大学
    • Year and Date
      2015-03-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] タンパク質リン酸化酵素NLKはShhシグナルの負の制御を介して後脳組織の構築を支える2015

    • Author(s)
      Shizuka Ishitani, Tohru Ishitani
    • Organizer
      第2回新学術領域「細胞競合」研究会議
    • Place of Presentation
      門司港ホテル、北九州市
    • Year and Date
      2015-01-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] New mechanisms that regulate Wnt⁄β-catenin signaling and their potential roles in cancer2014

    • Author(s)
      Tohru Ishitani
    • Organizer
      第73回日本癌学会総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-09-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Nemo-like kinase negatively regulates Hedgehog signaling in neural progenitor cells and brain tumor.2014

    • Author(s)
      Shizuka Ishitani, Tohru Ishitani
    • Organizer
      第20回小型魚類研究会口頭発表
    • Place of Presentation
      慶応義塾大学
    • Year and Date
      2014-09-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] Hipk2 and PP1c-mediated dephosphorylation of Dishevelled sustains Wnt signal transduction2014

    • Author(s)
      15.Nobuyuki Shimizu, Shizuka Ishitani, Atsushi Sato, Hiroshi Shibuya, Tohru Ishitani
    • Organizer
      11th International Conference on Zebrafish Development and Genetics
    • Place of Presentation
      Overture Center, Madison, USA.
    • Year and Date
      2014-06-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] タンパク質リン酸化酵素NLKによる神経前駆細胞の運命制御

    • Author(s)
      石谷 太、清水 誠之、石谷 閑
    • Organizer
      日本薬学会第134年会シンポジウム
    • Place of Presentation
      熊本大学
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] タンパク質リン酸化酵素NLKはShhシグナルの負の制御を介して後脳組織の構築を支える

    • Author(s)
      石谷 閑、清水 誠之、石谷 太
    • Organizer
      第三回細胞競合コロキウム
    • Place of Presentation
      北海道大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] Nemo-like kinase blocks Hedgehog signaling by phosphorylating Gli1 transcription factor in neural progenitor cells and brain tumor.

    • Author(s)
      Shizuka Ishitani, Nobuyuki Shimizu, Tohru Ishitani
    • Organizer
      第65回日本細胞生物学会年会シンポジウム
    • Place of Presentation
      ウインクあいち
    • Related Report
      2013 Annual Research Report
  • [Book] New Principles in Developmental Processes2014

    • Author(s)
      Ishitani T
    • Total Pages
      13
    • Publisher
      Springer
    • Related Report
      2013 Annual Research Report
  • [Remarks] 九州大学生体防御医学研究所細胞統御システム分野のホームページ

    • URL

      http://www.bioreg.kyushu-u.ac.jp/labo/crs/top.html

    • Related Report
      2014 Annual Research Report

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Published: 2013-05-21   Modified: 2022-01-27  

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