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Regulation of iron homeostasis by the p53-ISCU pathway.

Research Project

Project/Area Number 15K14377
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Tumor biology
Research InstitutionThe University of Tokyo

Principal Investigator

Tanikawa Chizu  東京大学, 医科学研究所, 助教 (30422421)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsp53 / 鉄代謝
Outline of Final Research Achievements

Accumulation of iron in tissues increases the risk of cancer, but iron regulatory mechanisms in cancer tissues are largely unknown. Here, we report that p53 regulates iron metabolism through the transcriptional regulation of ISCU (iron-sulfur cluster assembly enzyme), which encodes a scaffold protein that plays a critical role in Fe-S cluster biogenesis. HCT116 p53(+/+) cells were resistant to iron accumulation, but HCT116 p53(-/-) cells accumulated intracellular iron after DNA damage. Moreover, excess dietary iron caused significant elevation of serum iron levels in p53(-/-) mice. ISCU expression was decreased in the majority of human liver cancer tissues, and its reduced expression was significantly associated with p53 mutation. Our finding revealed a novel role of the p53-ISCU pathway in the maintenance of iron homeostasis in hepatocellular carcinogenesis.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (7 results)

All 2017 2016 2015

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 4 results,  Acknowledgement Compliant: 4 results) Presentation (3 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] EPSIN 3, A Novel p53 Target, Regulates the Apoptotic Pathway and Gastric Carcinogenesis.2017

    • Author(s)
      Mori J, Tanikawa C, Ohnishi N, Funauchi Y, Toyoshima O, Ueda K, Matsuda K.
    • Journal Title

      Neoplasia

      Volume: 19 Issue: 3 Pages: 185-195

    • DOI

      10.1016/j.neo.2016.12.010

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Regulation of myo-inositol biosynthesis by p53-ISYNA1 pathway2016

    • Author(s)
      Tomoyuki Koguchi, Chizu Tanikawa, Jinichi Mori, Yoshiyuki Kojima, Koichi Matsuda
    • Journal Title

      International Journal of Oncology

      Volume: 印刷中 Issue: 6 Pages: 2415-24

    • DOI

      10.3892/ijo.2016.3456

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Cystatin C as a p53‐inducible apoptotic mediator which regulates Cathepsin L activity2016

    • Author(s)
      Jinichi Mori, Chizu Tanikawa, Yuki Funauchi, Paulisally Hau Yi Lo, Yusuke Nakamura, Koichi Matsuda
    • Journal Title

      Cancer science

      Volume: 107 Issue: 3 Pages: 298-306

    • DOI

      10.1111/cas.12881

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Regulation of iron homeostasis by the p53-ISCU pathway2015

    • Author(s)
      Yuki Funauchi, Chizu Tanikawa, Paulisally Hau Yi Lo, Jinichi Mori, Yataro Daigo, Atsushi Takano, Yohei Miyagi, Atsushi Okawa, Yusuke Nakamura, Koichi Matsuda
    • Journal Title

      Scientific reports

      Volume: 5 Issue: 1 Pages: 16497-16497

    • DOI

      10.1038/srep16497

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] がん抑制遺伝子p53による制御経路の多角的網羅的探索から見えてきた新規がん抑制メカニズム2016

    • Author(s)
      谷川千津
    • Organizer
      日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] p53による転写制御の組織網羅的解析2015

    • Author(s)
      谷川千津、張、井元、山口、宮野、中川英刀、中村祐輔、松田浩一
    • Organizer
      日本癌学会学術集会
    • Place of Presentation
      名古屋国際会議場(愛知県・名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] Regulation of RNA processing by PADI4 pathway2015

    • Author(s)
      Chizu Tanikawa, Koji Ueda, Yusuke Nakamura, Koichi Matsuda.
    • Organizer
      AACR Annual Meeting
    • Place of Presentation
      Philadelphia, Pennsylvania, USA
    • Year and Date
      2015-04-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2018-03-22  

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