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Efficient cardiac induction of embryionic stem cells and induced pluripotent stem cells through regulation of ubiquitin-proteasome pathway.

Research Project

Project/Area Number 24591105
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

ASAKURA Masanori  独立行政法人国立循環器病研究センター, 研究開発基盤センター, 室長 (80443505)

Co-Investigator(Kenkyū-buntansha) KITAKAZE Masafumi  国立循環器病研究センター, 研究開発基盤センター, 部長 (20294069)
Research Collaborator MIN Kyung-Duk  
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords心筋分化 / ユビキチン / プロテアソーム系
Outline of Final Research Achievements

Heart failure is one of the leading causes of death in Japan and the novel diagnosis and treatment are strongly awaited. To overcome this issue, we aimed to elucidate the molecular mechanisms of cardiac induction in embryonic stem cells (ES cells). Comprehensive gene expression analysis using ES cells identified Asb2, which is thought to be an E3 ligase. Further analysis revealed that Asb2 is specifically expressed in the heart and skeletal muscle during development. In silico data base suggested potential interaction between Asb2 and Smad9, and we confirmed that Asb2 is the E3 ligase for Smad9 and leads it to proteasomal degradation. Our data suggested that Asb2-dependent Smad9 degradation plays important role in the development of the heart through quantitative regulation of Smad9 and thus the regulation of BMP signaling.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (4 results)

All 2014 Other

All Presentation (4 results)

  • [Presentation] Temporal and quantitative regulation of Smad9 by its specific ligase Asb2 is required for cardiac development through the induction of Tbx2 expression by BMP2 stimulation.2014

    • Author(s)
      Min KD, Asakura M, Ito S, Imazu M, Shindo K, Kitakaze M.
    • Organizer
      American Heart Association Scientific Sessions 2014, Best of AHA Specialty Conferences
    • Place of Presentation
      Chicago, U.S.A.,
    • Year and Date
      2014-11-15 – 2014-11-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] Pressure overload to the heart induces pulmonary up-regulation of genes coding secretory proteins involved in the cardiovascular diseases.2014

    • Author(s)
      Min KD, Asakura M, Ito S, Imazu M, Shindo K, Asanuma H, Kitakaze M.
    • Organizer
      ESC Congress 2014
    • Place of Presentation
      Barcelona,Spain
    • Year and Date
      2014-08-30 – 2014-09-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] Temporal and quantitative regulation of Smad9 by its specific ligase Asb2 is required for cardiac development through the induction of Tbx2 expression by BMP2 stimulation.2014

    • Author(s)
      Min KD, Asakura M, Ito S, Imazu M, Shindo K, Kitakaze M.
    • Organizer
      BCVS 2014
    • Place of Presentation
      Las Vegas, NV,,U.S.A.
    • Year and Date
      2014-07-14
    • Related Report
      2014 Annual Research Report
  • [Presentation] The E3 ligase Asb2 regulates cardiac development through targeting Smad9 for proteasomal degradation

    • Author(s)
      K.-D. Min, M.Asakura, et al.
    • Organizer
      第78回日本循環器学会学術集会
    • Place of Presentation
      東京国際フォーラム
    • Related Report
      2013 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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