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Basic research for development of new type of drugs based on the mechanism of transcriptional regulation

Research Project

Project/Area Number 06557127
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionThe University of Tokyo

Principal Investigator

HORIKOSHI Masami  The University of Tokyo, Institute of Molecular and Cellular Biosciences, Associate Professor, 分子細胞生物学研究所, 助教授 (70242089)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Tohru  The University of Tokyo, Institute of Molecular and Cellular Biosciences, Assist, 分子細胞生物学研究所, 助手 (10251480)
HASHIDA Ryouichi  Eizai Corp.Tsukuba Laboratory, Chief Researcher, 筑波研究所, 主任研究員
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥11,500,000 (Direct Cost: ¥11,500,000)
Fiscal Year 1995: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1994: ¥7,000,000 (Direct Cost: ¥7,000,000)
KeywordsTranscriptional regulation / Transcription factor / Interaction between DNA and transcription factors / Interaction between transcription factors / Development of drugs / Transcriptional regulatory factor / co-factor / two-hybrid system / TATAボックス結合因子 / TFIID / TFIIB / TBP / CTD / 転写基本因子
Research Abstract

Transcriptional regulation is carried out by the combination of various specific interactions such as DNA-protein and protein-protein interactions. Since transcription is the main reaction in regulating gene expression, the destruction of its regulatory mechanism may cause diseases. The research of this area is regarded as an appropriate target for new drug development. Our research includes the following.
1) Isolation of new type of transcription factors for drug development
In order to isolate new co-factors participating in DNA-protein and protein-protein interactions in transcriptional regulation, the two-hybrid screening system has been applied with the known factors as the probe. As a result, various factors have been isolated including candidate factors for sarcoma gene products and nuclear factors participating in autoimmune diseases. This methodology has been shown to be effective in the isolation of target factors for developing drugs.
2) Construction of a system for screening in drug development
As interactions between transcription factors can be detected by using two-hybrid screening system, the system is also thought to be adequate for the isolation of drugs which show inhibition activities on interactions. Other screening systems for drug development are under development, utilizing assays of transcriptional activity and the interactions between DNA and transcription factors.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (41 results)

All Other

All Publications (41 results)

  • [Publications] T. Kokubo et al.: "Molecular cloning of Drosophila TFIID subunits" Nature. 367. 484-487 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T. Kokubo et al.: "Interaction between the N-terminal domain of the 230-kDa subunit and the TATA box-binding subunit of TFIID negatively regulates TATA-box binding" Proc. Natl. Acad. Sci. U.S.A.91. 3520-3524 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T. K. Kim et al.: "Effects of activation-defective TBP mutations on transcription initiation in yeast" Nature. 369. 252-255 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] G. Mizuguchi et al.: "Independent control of transcription initiations from two sites by an intitator like element and TATA box in the human c-erbB-2 promoter" FEBS Lett.348. 80-88 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] F. Saito et al.: "Direct mapping of the human TATA box-binding protein(TBP) gene to 6q27 by fluorescence in situ hybridization" Jpn. J. Human Genet.39. 421-425 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] X. Tang et al.: "Cooperativity between an upstream TATA-like sequence and a CAA repeated element mediates EIA-dependent negative repression of the H-2K^b class I gene" J. Biol. Chem.270. 2327-2336 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] G. Mizuguchi et al.: "c-Myb repression of c-erbB-2 transcription by direct binding to the c-erbB-2 promoter" J. Biol. Chem.270. 9384-9389 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] D.- W. Gong et al.: "Molecular cloning of cDNA encoding the small subunit of Drosophila transcription initiation factor TFIIF" Nucleic acids Res.23. 1882-1886 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T. Umehara et al.: "Isolation of a cDNA encoding a mouse TFIID subunit containing histone H4 homology" Gene. 161. 301-302 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S. Kida et al.: "Three distinct regions in a rat TFIID subunit containing histone H4 homology" Gene. 161. 303-304 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T. Yamamoto et al.: "Rapid preparation of plasmid templates suitable for a DNA sequencer without RNase treatment" Nucleic Acids Res.23. 3351-3352 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K. Hisatake et al.: "Evolutionary conservation of human TATA-binding-polypeptide-associated factors TAFII31 and TAFII80 and interactions of TAFII80 with other TAFs and with general" Proc. Natl. Acad. Sci. U.S.A.92. 8195-8199 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T. Ohkuma et al.: "Analysis of the role of TFIIE in basal transcription and TFIIH-mediated carboxy-teminal domain phosphorylation through structure-function studies of TFIIE-α" Mol. Cell. Biol.15. 4856-4566 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S. Hasegawa et al.: "A Sequence of a Xenopus laevis TFIID subunit rebeals remarkable conservation among vertebrates" Gene. 164. 369-370 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T. Umehara et al.: "Isolation and characterization of a cDNA encoding a new type of human transcription elongation factor S-II" Gene. 167. 297-302 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Kokubo, D.-W.Gong, J.C.Wootton, M.Horikoshi, R.G.Roeder & Y.Nakatani: "Molecular cloning of Drosophila TFIID subunits" Nature. 367. 484-487 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Kokubo, S.Yamashita, M.Horikoshi, R.G.Roeder & Y.Nakatani: "Interaction between the N-terminal domain of the 230-kDa subunit and the TATA box-binding subunit of TFIID negatively regulates TATA-box binding" Proc.Natl.Acad.Sci.U.S.A.91. 3520-3524 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.K.Kim, S.Hashimoto, R.J.Kelleher III,P.M.Flanagan, R.D.Kornberg, M.Horikoshi & R.G.Roeder: "Effects of activation-defective TBP mutations on transcription initiation in yeast" Nature. 369. 252-255 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] G.Mizuguchi, C.Kanei-Ishii, T.Sawazaki, M.Horikoshi, R.G.Roeder, T.Yamamoto & S.Ishii: "Independent control of transcription initiations from two sites by an initiator-like element and TATA box in the human c-erbB-2 promoter" FEBS Lett. 348. 80-88 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] F.Saito, T.Yamamoto, M.Horikoshi & T.Ikeuchi: "Direct mapping of the human TATA box-binding protein (TBP) gene to 6q27 by fluorescence in situ hybridization" Jpn.J.Human Genet. 39. 421-425 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] X.Tang, H.-O.Li, O.Sakatsume, T.Ohta, H.Tsutsui, A.F.A.Smit, M.Horikoshi, P.Kourilsky, A.Israel, G.Gachelin & K.Yokoyama: "Cooperativity between an upstream TATA-like sequence and a CAA repeated element mediates E1A-dependent negative repression of the H-2K^b class I gene" J.Biol.Chem.270. 2327-2336 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] G.Mizuguchi, C.Kanei-Ishii, T.Takahashi, T.Yasukawa, T.Nagase, M.Horikoshi, T.Yamamoto & S.Ishii: "c-Myb repression of c-erbB-2 transcription by direct binding to the c-erbB-2 promoter" J.Biol.Chem.270. 9384-9389 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] D.-W.Gong, M.A.Mortin, M.Horikoshi & Y.Nakatani: "Molecular cloning of cDNA encoding the small subunit of Drosophila transcription initiation factor TFIIF" Nucleic Acids Res.23. 1882-1886 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Umehara, S.Kida & M.Horikoshi: "Isolation of a cDNA encoding a mouse TFIID subunit containing histone H4 homology" Gene. 161. 301-302 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S.Kida, T.Umehara & M Horikoshi: "Three distinct regions in a rat TFIID subunit containing histone H4 homology" Gene. 161. 303-304 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Yamamoto & M.Horikoshi: "Rapid preparation of plasmid templates suitable for a DNA sequencer without RNase treatment" Nucleic Acids Res.23. 3351-3352 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Hisatake, T.Ohta, R.Takada, M.Guermah, M.Horikoshi, Y.Nakatani, & R.G.Roeder: "Evolutionary conservation of human TATA-binding-polypeptide-associated factors TAFII31 and TAFII80 and interactions of TAFII80 with other TAFs and with general transcription factors" Proc.Natl.Acad.Sci.U.S.A.92. 8195-8199 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Ohkuma, S.Hashimoto, C.K.Wang, M.Horikoshi & R.G.Roeder: "Analysis of the role of TFIIE in basal transcription and TFIIH-mediated carboxy-terminal domain phosphorylation through structure-function studies of TFIIE-alpha" Mol.Cell.Biol.15. 4856-4866 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S.Hasegawa, T.Kuzuhara & M.Horikoshi: "A Sequence of a Xenopus laevis TFIID subunit reveals remarkable conservation among vertebrates" Gene. 164. 369-370 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Umehara, S.Kida, T.Yamamoto & M.Horikoshi: "Isolation and characterization of a cDNA encoding a new type of human transcription elongation factor S-II" Gene. 167. 297-302 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] X. Tang et al.: "Cooperativity between and upstream TATA-like sequence and a CAA repeated element mediates E1A-dependent negative repression of the H-2K^b class lgene" J. Biol. Chem.270. 2327-2336 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] G. Mizuguchi et al.: "c-Myb repression of c-erbB-2 transcription by direct binding to the c-erbB-2 promoter" J. Biol. Chem.270. 9384-9389 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] T. Umehara et al.: "Isolation of a cDNA encoding a mouse TFIID subunit containing histone H4 homology" Gene. 161. 301-302 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] T. Yamamoto et al.: "Rapid preparation of plasmid templates suitable for a DNA sequencer without RNase treatment" Nucleic Acids Res.23. 3351-3352 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] K. Hisatake et al.: "Evolutionary conservation of human TATA-binding-polypeptide-associated factors TAFII31 and TAFII80 and interactions of TAFII80 with other TAFs and with general transcription factors" Proc Nat1. Acad. Sci. U. S. A.92. 8195-8199 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] T. Umehara et al.: "Isolation and characterization of a cDNA encoding a new type of human transcription elongation factor S-II" Gene. 167. 297-302 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] T.Kokubo et al.: "Molecular cloning of Drosophila TFIID subunits" Nature. 367. 484-487 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Kokubo et al.: "Interaction between the N-terminal domain of the 230-kDa subunit and the TATA box-binding subunit of TFIID negatively regulates TATA-box binding" Proc.Natl.Acad.Sci.U.S.A.91. 3520-3524 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.K.Kim et al.: "Effects of activation-defective TBP mutations on transcription initiation in yeast" Nature. 369. 252-255 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] G.Mizuguchi et al.: "Independent control of transcription initiations from two sites by an initiator-like element and TATA box in the human c-erbB-2 promoter" FEBS Lett.348. 80-88 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] F.Saito et al.: "Direct mapping of the human TATA box-binding protein(TBP) gene to 6q27 by fluorescence in situ hybridization" Jpn.J.Human Genet.39. 421-425 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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