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Development of a novel treatment for immunoregulation by analyzing specific regulatory mechanisms of the NFAT family.

Research Project

Project/Area Number 24590107
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biological pharmacy
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

KITAMURA Noriko  公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 研究員 (80415603)

Co-Investigator(Kenkyū-buntansha) KAMINUMA Osamu  公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 主任研究員 (80342921)
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: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsNFAT / CN / 免疫抑制薬 / 新規免疫抑制薬
Outline of Final Research Achievements

Since numerous side effects of CN inhibitors are mostly caused by the diversity of the NFAT family, control of a part, not all, of the function of NFAT family members is desirable. By comparing the binding activity of CN with each NFAT, we identified a new CN-binding region into NFATc1. The CN-binding affinity of this region was much different among the NFAT family. By means of competition assay using sequential partial peptides, we determined the core peptide and essential amino acids in it. By analyzing the gene expression in NFATc4-siRNA expressing cells, and the NFATc4 promoter activity in siRNA library-transfected cells, several candidate molecules related with the selectivity among NFAT family members were identified. The molecular mechanisms useful for the regulation of a part of NFAT family members were clarified.

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 2012 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (3 results)

  • [Journal Article] NFAT1 and NFAT2 differentially regulate IL-17A expression in human T cells.2012

    • Author(s)
      Kaminuma O, Kitamura N, Mori A, Tatsumi H, Nemoto S, Hiroi T.
    • Journal Title

      Int Arch Allergy Immunol

      Volume: 158 Issue: Suppl. 1 Pages: 30-34

    • DOI

      10.1159/000337757

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Diversity of nuclear factor of activated T cells in vertebrate organisms.2014

    • Author(s)
      Kaminuma O, Kitamura N, Hiroi T.
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      2014-10-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] Selective down-regulation of IL-2-mediated cytokine expression in human T cells by protein phosphatase 1 inhibitors.2014

    • Author(s)
      Kaminuma O, Kitamura N, Mori A, Hiroi T.
    • Organizer
      Experimental Biology 2014
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2014-04-30
    • Related Report
      2014 Annual Research Report
  • [Presentation] Differential contribution of calcineurin-binding regions among NFAT family members.

    • Author(s)
      Kaminuma O, Kitamura N, Nemoto S, Tatsumi H, Mori A, Hiroi T.
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report

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

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