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Domain Structure of Transcription factors which act as a Redox sensor, and its mechanism of nuclear export.

Research Project

Project/Area Number10680649
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Molecular biology
Research InstitutionThe University of Tokyo

Principal Investigator

KUGE Shusuke  The Institute of Medical Science, The University of Tokyo, Lecturer, 医科学研究所, 講師 (50186376)

Project Period (FY) 1998 – 1999
Project Status Completed(Fiscal Year 1999)
Budget Amount *help
¥2,900,000 (Direct Cost : ¥2,900,000)
Fiscal Year 1999 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1998 : ¥2,300,000 (Direct Cost : ¥2,300,000)
KeywordsYAP1 / Crm1 / Nuclear export / Oxidative stress / Budding yeast / Transcription factor / Molecular biology / 分子生物 / yAP-1
Research Abstract

Yap1 is AP-1 like transcript ion factor of the budding yeast, S. cerevisiae. Yap1 is a crucial and essential transcription factor for the oxidative stress response. We have shown previously that Yap1 mainly exists in the cytoplasm, however, Yap1 localized in the nucleus in response to oxidative stress.
In this research project, we aim to show that the mechanism of the regulation of nucleo-cytoplasmic transport of Yap1. Firstly, we showed that Yap1 is imported by one of the multiple import receptors (importin), Pse1, which is shown to be import receptor for unrelated transcription factor Pho4. On the other hand, Yap I is exported by nuclear export receptor (exportin) Crm1 that recognizes the nuclear export signal (NES). Therefore, Yap1 shuttles between the cytoplasm and nucleus. The nuclear export contributes lower concentration of Yap1 in the nucleus, and thus the lower activity of target gene transcription. Interestingly, our data indicates that oxidative stress inhibits ,the interaction between Yap1 and the Crm1.
Secondly, CRD (C-terminal cysteine-rich domain of Yap1, appears to be essential domain for Crm1-dependent nuclear export, indicating that CRD acts as a NES. The CRD contains NES-like hydrophobic cluster as well as unique three cysteine residues, one in the middle of NES-like region. When all three cysteine residues are mutated to Thr or Ala. CRD can act as NES, however, no more oxidative stress response was observed.
Thirdly, we showed that cysteine residues in the CRD appear to be oxidized to disulfide and form CRD-CRD homo-dimer. These suggest that the CRD cysteine residues are redox regulated, and the NES activity might be inhibited by the disulfide formation.

Report

(3results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report

Research Products

(23results)

All Other

All Publications

  • [Publications] Mark W. Toone: "Stress-dependent activation of the fission yeast transcription factor, Pap 1"Genes and Development. 12(10). 1453-1463 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shusuke Kuge: "Crm1 (XpoI) dependent nuclear export of the budding yeast transcription factor yAP-1 is sensitive to oxidative stress"Genes to Cells. 3(8). 521-532 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kazuko Shiroki: "Intracellular redistribution of truncated La protein produced by poliovirus 3Cpro-mediated cleavage"J. Virol.. 73. 2193-2200 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nobuhiko Miura: "Overexpression of L-glutamine: D-fructose-6-phosphate amidotransferase provided resistance to methylmercury in Saccharomyces cerevisiae"FEBS Lett.. 458. 215-218 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Akira Naganuma: "GFAT as a Target Molecule of Methylmercury Toxicity in Saccharomyces cerevisiae"FASEB J. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 久下周佐: "転写因子の核局在機構-酸化ストレスによるyAP-1の核外輸送阻害"蛋白質核酸酵素. 44(5). 668-675 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shusuke Kuge: "Oxygen Radicals, Redox Regulation of Signaling and Disease Control by Antioxidant"Marcel Dekker. 11 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Toone, W. M., Kuge, S., Samuels, M., Morgan, B. A., Toda, T. and Jones, N.: "Stress-dependent activation of the fission yeast transcription factor, Pap1."Genes and Development. 12. 1453-1463 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S. Kuge, T. Toda, N. Iizuka and A. Nomoto.: "Crm1 (XpoI) dependent nuclear export of the budding yeast transcription factor yAP-1 is sensitive to oxidative stress."Genes to Cells. 3. 521-532 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Shiroki, T. Isoyama, S. Kuge, T. Ishii, S. Ohmi, S. Hata, K. Suzuki, Y. Takasaki and A. Nomoto.: "Intracellular redistribution of truncated La protein produced by poliovirus 3Cpro-mediated cleavage."J. Virol.. 73. 2193-2200 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miura, N., Kaneko, S., Hosoya, S., Furuchi, T., Miura, K., Kuge, S. and Naganuma, A.: "Overexpression of L-glutamine : D-fructose-6-phosphate amidotransferase provides resistance to methylmercury in Saccharomyces cerevisiae."FEBS Lett.. 458. 215-218 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Naganuma, A., Miura, N., Kaneko, S., Mishina, T., Hosoya, S., Miyairi, S., Furuchi, T. and Kuge, S.: "GFAT as a Target Molecule of Methylmercury Toxicity in Saccharomyces cerevisiae."FASEB J.. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mark W. Toone: "Stress-dependent activation of the fission yeast transcription factor, Pap1."Genes and Development. 12(10). 1453-1463 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shusuke Kuge: "Crm1 (XpoI) dependent nuclear export of the budding yeast transcription factor yAP-1 is sensitive to oxidative stress."Genes to Cells. 3(8). 521-532 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kazuko Shiroki: "Intracellular redistribution of truncated La protein produced by poliovirus 3Cpro-mediated clevage"J. Virol.. 73(3). 2193-2200 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nobuhiko Miura: "Overexpression of L-glutamine : D-fructose-6-phosphate amidotransferase provides resistance to methylmercury in Saccharomyces cerevisiae"FEBS Lett.. 458(2). 215-218 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akira Naganuma: "GFAT as a Target Molecule of Methylmercury Toxicity in Saccharomyces cerevisiae"FASEB J. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 久下 周佐: "転写因子の核局在機構―酸化ストレスによるyAP-1の核外輸送阻害"蛋白質核酸酵素. 44(5). 668-675 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shusuke Kuge: "Oxygen Radicals, Redox Regulation of Signaling and Disease Control by Antioxidant"Marcel Dekker.. 328 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Mark W.Toone: "Stress-dependent activation of the fission yeast transcription factor,Pap 1." Genes and Development. 12 (10). 1453-1463 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shusuke Kuge: "Crm1(XpoI)dependent nuclear export of the budding yeast transcription factor yAP-1 is sensitive to oxidative stress." Genes to Cells. 3 (8). 521-532 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kazuko Shiroki: "Intracellular redistributionof truncated La protein produced by poliovirus 3Cpromediated clevage." J.Virol.(in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shusuke Kuge: "Oxygen Radicals,Redox Regulation of Signaling and Disease" Marcel Dekker (in press), (1999)

    • Related Report
      1998 Annual Research Report

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Published : 1998-04-01   Modified : 2016-04-21  

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