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A novel cascade of TGF-β signaling dependent on mitochondrial reactive oxygen species and its biological significance

Research Project

Project/Area Number 19570185
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionShowa University

Principal Investigator

SHIBANUMA Motoko  Showa University, 薬学部, 教授 (60245876)

Co-Investigator(Kenkyū-buntansha) KANEYAMA Syuri  昭和大学, 薬学部, 助教 (10338535)
MORI Kazunori  昭和大学, 薬学部, 助教 (60349040)
NOSE Iyoshi  昭和大学, 薬学部, 客員教授 (70012747)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
KeywordsTGFβ / マトリックスメタロプロテアーゼ / ミトコンドリア / MMP9 / 遺伝子発現 / matrix metalloproteinase
Research Abstract

TGFβによる悪性化形質関連遺伝子MMP-9の転写制御機構について、主にマウス乳腺上皮細胞を用い、関与する転写因子をsiRNAによるスクリーニングにより検索した。その結果、cAMP応答配列結合因子(CREB)がMMP9の転写をHDAC3などその他の転写共役因子とともに負に制御する可能性が示唆された。また、TGFβ刺激によりミトコンドリアからの活性酸素産生が上昇し細胞内が酸化状態に傾くが、この変化がシグナルとして重要であった。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (17 results)

All 2009 2008 2007 Other

All Journal Article (10 results) (of which Peer Reviewed: 7 results) Presentation (7 results)

  • [Journal Article] Competitive nuclear export of cyclin D1 and Hic-5 regulates anchorage-dependence of cell growth and survival2009

    • Author(s)
      Kazunori Mori, Etsuko Hirao, Yosuke Toya, Yukiko Oshima, Fumihiro Ishikawa, Kiyoshi Nose, Motoko Shibanuma
    • Journal Title

      Mol. Biol Cell. 20

      Pages: 218-232

    • Related Report
      2008 Final Research Report
  • [Journal Article] Competitive nuclear export of cyclin D1 and Hic-5 regulates anchorage-dependence of cell growth and survival.2009

    • Author(s)
      Mori, K., et al.
    • Journal Title

      Mol. Biol Cell. 20

      Pages: 218-232

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene expression profiling identifies a role for CHOP during inhibition of the mitochondrial respiratory chain.2009

    • Author(s)
      Ishikawa, F., et al.
    • Journal Title

      J. Biochem. in press

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Downregulation of hepatocyte nuclear factor-4α and its role in regulation of gene expression by TGF-β in mammary epithelial cells2008

    • Author(s)
      Fumihiro, Ishikawa, Takashi Akimoto, Haruka Yamamoto, Yuri Araki, Toshihiko Yoshie, Kazunori Mori, Hidetoshi Hayashi, Kiyoshi Nose, Motoko Shibanuma
    • Journal Title

      Exp. Cell Res. 314

      Pages: 2131-2141

    • Related Report
      2008 Final Research Report
  • [Journal Article] Downregulation of hepatocyte nuclear factor-4. and its role in regulation of gene expression by TGF-・in mammary epithelial cells.2008

    • Author(s)
      Ishikawa, F., et al.
    • Journal Title

      Exp. Cell Res. 314

      Pages: 2131-2141

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Competitive nuclear export of cyclin Dl and Hic-5 regulates anchorage-dependence of cell growth and survival2008

    • Author(s)
      Mori, K., et. al.
    • Journal Title

      J. Cell Biol. (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Downregulation of hepatocyte nuclear factor-4・and its role in regulation of gene expression by TGF-・ in mammary epithelial cells2008

    • Author(s)
      Ishikawa, F., et. al.
    • Journal Title

      Exp.Cell Res. (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of matrix metalloprotease gene expression in an endothelial cell line by direct interaction with malignant cells2007

    • Author(s)
      Hasebe, Y., et. al.
    • Journal Title

      Cancer Sci. 98

      Pages: 58-67

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of Jumping translocation breakpoint (JTB) gene product isolated as a TGF-β-inducible clone involved in regulation of mitochondrial function,cell growth and death2007

    • Author(s)
      Kanome, T., et. al.
    • Journal Title

      Oncogene 26

      Pages: 5991-6001

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene expression profiling identifies a role for CHOP during inhibition of the mitochondrial respiratory chain

    • Author(s)
      Fumihiro Ishikawa, Kiyoshi Nose, Motoko Shibanuma
    • Journal Title

      J. Biochem. (Epub ahead of print)

    • NAID

      10025187713

    • Related Report
      2008 Final Research Report
  • [Presentation] Transcriptional induction of MMP10 by TGFβ mediated by MEF2 and class IIa HDACs2009

    • Author(s)
      Fumihiro Ishikawa, Emi Kaneko, Toshihiko Yoshie, Kiyoshi Nose, and Motoko Shibanuma
    • Organizer
      Keystone Symposia
    • Place of Presentation
      Vancouver, British Columbia, Canada.
    • Year and Date
      2009-03-17
    • Related Report
      2008 Final Research Report
  • [Presentation] MMP9の発現制御に特異的に関わる新規TGFβ転写制御機構の解析2008

    • Author(s)
      三瓶瑠利子、石川文博、野瀬清、柴沼質子
    • Organizer
      第31回日本分子生物学会年会 第81回日本生化学会大会 合同大会
    • Place of Presentation
      神戸ポートアイランド
    • Related Report
      2008 Final Research Report
  • [Presentation] TGFβによるMEF2とClassIIaHDACを介したMMP10転写制御機構2008

    • Author(s)
      石川文博、野瀬清、柴沼質子
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Related Report
      2008 Final Research Report
  • [Presentation] TGFβによるMEF2とClassIIaHDACを介したIMP10転写制御機構2008

    • Author(s)
      石川文博, 他
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Related Report
      2008 Annual Research Report
  • [Presentation] MMP9の発現制御に特異的に関わる新規TGFβ転写制御機構の解析2008

    • Author(s)
      三瓶瑠利子, 他
    • Organizer
      31回日本分子生物学会年会第81回日本生化学会大会合同大
    • Place of Presentation
      神戸ポートアイランド
    • Related Report
      2008 Annual Research Report
  • [Presentation] ミトコンドリア機能の変化と細胞の悪性化形質誘導2007

    • Author(s)
      柴沼 質子
    • Organizer
      第30回日本分子生物学会、第80回日本生化学会、合同大会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] TGFβによるHepatocyte nuclear factor 4α発現制御機構及び上皮問葉系転換におけるその生物学的意義の解析2007

    • Author(s)
      石川 文博
    • Organizer
      第30回日本分子生物学会、第80回日本生化学会、合同大会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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