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Elucidation of the gene expression mechanism by the heme -Bach2 pathway

Research Project

Project/Area Number 16K08573
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General medical chemistry
Research InstitutionTohoku University

Principal Investigator

MASTUI Miki  東北大学, 医学系研究科, JSPS特別研究員(RPD) (00455784)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsヘム / 遺伝子発現 / 遺伝子発現制御 / 天然変性タンパク質
Outline of Final Research Achievements

Transcription factor Bach2 possess BTB and bZip domains, separated by long unstructured sequences. In addition, Bach2 protein contains a conserved Cys-Pro motif, which has been identified as the heme-binding site. Our previous studies of Bach2 revealed that when heme binding occurs in the intrinsically disordered region, the conformation of the region is altered. In this study, we identified the serine-threonine kinase, which directly bound to intrinsically disordered region of Bach2. This kinase inhibitor induced the cytoplasmic and nuclear localization of Bach2. Moreover, this kinase inhibitor acts on the repression activity of Bach2. The LC-MS/MS analysis of phosphorylated-site of Bach2 by this kinase in the presence or absence of heme showed that heme changed the phosphorylated-site of Bach2. These results suggested that heme regulates phosphorylated-site of intrinsically disordered region of Bach2 and releases of transcriptional repression activity of Bach2.

Academic Significance and Societal Importance of the Research Achievements

本研究の特色は、研究対象であるBach2 が液性免疫における形質細胞分化、自然免疫におけるマクロファージの分化に重要な転写因子であり、かつBach2 が複数のヘムに制御される天然変性タンパク質であるという点にある。ヘムタンパク質の多くは安定な立体構造をとり、ヘムとタンパク質が1:1 で結合して機能しているものがほとんどである。これまでに、ヘムにより制御される天然変性タンパク質の報告はない。本研究によって、生体内でヘム濃度変化が液性免疫および自然免疫の重要なシグナル因子となる可能性が示された。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (5 results)

All 2019 2018 2017 2016

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (3 results)

  • [Journal Article] Functional Heme Binding to the Intrinsically Disordered C-Terminal Region of Bach1, a Transcriptional Repressor2019

    • Author(s)
      Segawa, K., Watanabe-Matsui, M., Matsui, T., Igarashi, K. and Murayama, K.
    • Journal Title

      The Tohoku Journal of Experimental Medicine

      Volume: 247 Issue: 3 Pages: 153-159

    • DOI

      10.1620/tjem.247.153

    • NAID

      130007610254

    • ISSN
      0040-8727, 1349-3329
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phosphorylation of BACH1 switches its function from transcription factor to mitotic chromosome regulator and promotes its interaction with HMMR.2018

    • Author(s)
      Li J, Shima H, Nishizawa H, Ikeda M, Brydun A, Matsumoto M, Kato H, Saiki Y, Liu L, Watanabe-Matsui M, Iemura K, Tanaka K, Shiraki T, Igarashi K.
    • Journal Title

      Biochemical Journal

      Volume: 475 Issue: 5 Pages: 981-1002

    • DOI

      10.1042/bcj20170520

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] ヘムシグナルによる天然変性タンパク質Bach2の制御機構と生理学的意義の解明2017

    • Author(s)
      松井 美紀、島 弘季、武藤哲彦、松本光代、 村山 和隆、五十嵐 和彦
    • Organizer
      ConBio2017(生命科学系学会合同年次大会)、神戸
    • Related Report
      2017 Research-status Report
  • [Presentation] ヘムによる転写因子Bach2天然変性領域の制御機構の解明2016

    • Author(s)
      松井美紀、島弘季、上島珠美、白水美香子、村山和隆、五十嵐和彦
    • Organizer
      第89回 日本生化学学会
    • Place of Presentation
      仙台国際センター(仙台)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
  • [Presentation] ヘム結合転写抑制因子Bach2の制御機構の解明2016

    • Author(s)
      松井美紀、島弘季、上島珠美、白水美香子、村山和隆、五十嵐和彦
    • Organizer
      第16回 日本蛋白質科学学会年会
    • Place of Presentation
      福岡国際会議場(福岡)
    • Year and Date
      2016-06-07
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2021-02-19  

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