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INHIBITOR MOLECULAR BIOLOGY FOR ELUCIDATION OF CHROMATIN FUNCTION (1998)

Research Project

Project/Area Number 09460045
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用微生物学・応用生物化学
Research InstitutionTHE UNIVERSITY OF TOKYO

Principal Investigator

YOSHIDA Minoru  DEPARTMENT OF BIOTECHNOLOGY,GRADUATE SCHOOL OF AGRICULTURE AND LIFE SCIENCE,THE UNIVERSITY OF TOKYO,ASSOCIATE PROFESSOR, 大学院・農学生命科学研究科, 助教授 (80191617)

Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥16,200,000 (Direct Cost: ¥16,200,000)
Fiscal Year 1998: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1997: ¥12,600,000 (Direct Cost: ¥12,600,000)
Keywordschromatin / histone / acetylation / nuclear export / trichostatin / leptomycin / CRM1 / transcription / ヒストンアセチル化 / 細胞周期 / CDK
Research Abstract

phd1^+, the first histone deacetylase gene from fission yeast Schizosaccharomyces pombe, was cloned. The gene was required for the onset of meiotic cell cycle and resistance to trichostatin A (TSA), a histone deacetylase inhibitor. RT-PCR and Western blot analyses revealed that p2lWaf1, a cyclin-dependent kinase inhibitor, was induced in mammalian cells in response to TSA.The enhanced expression was independent of p53, a major tumor suppressor protein, suggesting that p21 induction is responsible for TSA-induced cell cycle arrest. A human homolog of ORM1, the target protein of leptomycin B (LMB), was cloned. We showed that CRM1 is a receptor for the nuclear export signal (NES) of proteins, and that LMB directly binds CRM1 to inhibit its function. Using LMB, we demonstrated that Pap1, a fission yeast AP-1 like transcription factor, contained NES in the C-terminal region, which is responsible for its cytoplasmic localization.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Kudo et al.: "Leptomycin B inhibition of signal-mediated nuclear export by direct binding to CRM1." Exp.Cell Res.242. 540-547 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kim et al.: "phdl+,a histone deacetylase gene of Schizosaccharomyces pombe,is required for the meiotic cell cycle and resistance to trichostatin A." FEBS Lett.436. 193-196 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakajima et al.: "FR901228,a potent antitumor antibiotic, is a novel histone deacetylase inhibitor." Exp.Cell Res.241. 126-133 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ki et al.: "Identification of radicicol as an inhibitor of in vivo Ras/Raf interaction by the yeast two-hybrid screen system." J.Antibiot.51. 936-944 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshida et al.: "Leptomycin,an antifungal and antitumor Streptomyces metabolite,is a novel chemical probe for eukaryotic nucleo-cytoplasmic transport." Actinomycetologica. 12. 120-128 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kudo et al.: "A novel nuclear export signal sensitive to oxidative stress in the fission yeast transcription factor Pap1." J.Biol.Chem.(印刷中). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshida, M.and Horinouchi S: "G proteins,Cytoskeleton and Cancer." R.G.Landes, 342 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kudo, N., Wolff, B., Sekimoto, T., Schreiner, E.P., Yoneda, Y., Yanagida, M., Horinouchi, S., and Yoshida, M.: "Leptomycin B inhibition of signal-mediated nuclear export by direct binding to CRM1." Exp.Cell Res.242. 540-547 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakajima, H., Kim, Y.B., Terano, H., Yoshida, M., and Horinouchi, S.: "FR901228, a potent antitumor antibiotic, is a novel histone deacetylase inhibitor." Exp.Cell Res.241. 126-133 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kim, Y.B., Honda, A., Yoshida, M., and Horinouchi, S.: "phd1^+, a histone deacetylase gene of Schizosaccharomyces pombe, is required for the meiotic cell cycle and resistance to trichostain A." FEBS Lett.436. 193-196 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ki, S.W., Kasahara, K., Kwon, H.J., Eishima, J., Takasako, K., Cooper, J.A., Yoshida, M., and Horinouchi, S.: "Identification of radicicol as an inhibitor of in vivo Ras/Raf interaction by the yeast two-hybrid screen system." J.Antibiot.51. 936-944 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshida, M., Kudo, N., Taoka, H., Akakura, S., and Horinouchi, S.: "Leptomycin, an antifungal and antitumor Streptomyces metabolite, is a novel chemical probe for eukaryotic nucleo-cytoplasmic transport." Actinomycetologica. 12. 120-128 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kudo, N., Taoka, H., Toda, T., Yoshida, M., and Horinouchi, S.: "A novel nuclear export signal sensitive to oxidative stress in the fission yeast transcription factor Pap1." J.Biol.Chem.(in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kose, S., Imamoto, N., Tachibana, T., Yoshida, M., and Yoneda, Y.: "beta-Subunit of nuclear pore-targeting complex (importin-beta) can be exported from the nucleus in a Ran-unassisted manner." J.Biol.Chem.(in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Inokoshi, J., Katagiri, M., Arima, S., Tanaka, H., Hayashi, M., Kim, Y.B., Furumai, R., Yoshida, M., Horinouchi, S., and Omura, S.: "Neuronal differentiation of Neuro 2a cells by inhibitors of cell progression, trichostatin A and butyrolactone I." Biochem.Biophys.Res.Commun.(in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kim, Y.B., Lee, K.-H., Sugita, K., Yoshida, M., and Horinouchi, S.: "Oxamflatin is a novel antitumor compound that inhibits mammalian histone deacetylase." Oncogene. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sano, M., Yoshida, M., Fukui, S., and Kitajima, S.: "Radicicol potentiates neurotrophin-mediated neurite outgrowth and survival of cultured sensory neurons from chick embryo." J.Neurochem.(in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Niki, T., Rombouts, K., De Bleser, P., Schuppan, D., Yoshida, M., Gabbiani, G., and Geerts, A.: "A histone deacetylase inhibitor, trichostatin A,suppresses myofibroblastic differentiation of rat hepatic stellate cells in primary culture." Hepatology. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kudo et al.: "Molecular cloning and cell cycle-dependent expression of mammalian CRM1, a protein involved in nuclear export of proteins." J.Biol.Chem.272. 29742-29751 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fornerod et al.: "CRM1 is an export receptor for leucine-rich nuclear export signals." Cell. 90. 1051-1060 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fukuda et al.: "CRM1 is responsible for intracellular transport mediated by the nuclear export signal." Nature. 390. 308-311 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kudo et al.: "Leptomycin B inhibition of signal-mediated nuclear export by direct binding to CRM1." Exp.Cell Res.242. 540-547 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kim et al.: "phd1+, a histone deacetylase gene of Schizosaccharomyces pombe, is required for the meiotic cell cycle and resistance to trichostatin A." FEBS Lett.436. 193-196 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakajima et al.: "FR901228, a potent antitumor antibiotic, is a novel histone deacetylase inhibitor." Exp.Cell Res. 241. 126-133 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yoshida, M. and Horinouchi S: "G proteins, Cytoskeleton and Cancer." R.G.Landes, 342 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Yoshida et al.: "Biochemical differences between staurosporine-induced apoptosis and premature mitosis" Experimental Cell Reseach. 232. 225-239 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] N.Kudo et al.: "Molecular cloning and cell cycle-dependent expression of mammalian CRM1,a protein involved in nuclear export of proteins" Journal of Biological Chemistry. 272. 29742-29751 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Fornerod et al.: "CRM1 is an export receptor for leucine-rich nuclear export signals" Cell. 90. 1051-1060 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Fukuda et al.: "CRM1 is responsible for intracellular transport mediated by the nuclear export signal" Nature. 390. 308-311 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] H.J.Kwon et al.: "Suppression of morphological transformation by radicicol is accompanied by enhanced gelsolin expression" Oncogene. 15. 2625-2631 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Kasahara et al.: "Identification of preassin as a selective inhibitor for cell growth of the fission yeast ts mutants defective in cdc2-regulatory genes." Journal of Autibiotics. 50. 267-269 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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