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Molecular cloning of trans-acting factor cDNA for IFN-gamma-inducible indoleamine 2,3-dioxygenase

Research Project

Project/Area Number 04680203
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 代謝生物化学
Research InstitutionOsaka Bioscience Institute

Principal Investigator

TAKIKAWA Osamu  Osaka Bioscience Institute, Department of Cell Biology, Research Scientist, 第4研究部, 研究員 (70163342)

Co-Investigator(Kenkyū-buntansha) TONE Sigenobu  Wakayama MEdical College Department of Biochemistry, Assistant Professor, 助手 (70211399)
YOSHIDA Ryotaro  Osaka Bioscience Institute, Department of Cell Biology, Head, 第4研究部, 部長 (10124760)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1992: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsOxygenase / Interferon-gamma / Trans-acting factor / Signal transduction / Cytokine / Tryptophan metabolism / インターフェロン-γ / インターフェロンーγ / 誘導酵素 / 分子生物学 / 細胞内情報伝達
Research Abstract

Until 1992, we have isolated the gene of indoleamine 2,3-dioxygenase (IDO), an IFN-gamma-inducible tryptophan degrading enzyme, from human genomic DNA library using the IDO cDNA as a probe, and their restriction maps and partial nucleotide sequences were determined. The 5' flanking region contains IFN-stimulated response element (ISRE) and X-box like sequences. These sequences have a promoting activity for transcription of IDO mRNA.The IFN-gamma-mediated production of the IDO mRNA was suppressed by protein synthesis inhibitors, indicating an involvement of protein(s) newly synthesized in the induction of mRNA.The synthesis of the protein(s) occurred within 3h after the addition of IFN-gamma.
In 1993, we have examined the presence of trans-acting protein(s) for the enhancer element (ISRE and X-box) for transcription of IDO mRNA in nuclear or cytoplasmic extract of human lung fibroblasts (HEL), which exhibited the highest induction of IDO by the addition of IFN-gamma. On the other hand, the expression of IDO gene was inhibited strongly by herbimycin A, an inhibitor for tyrosine kinase, suggesting an implication of a tyrosine kinase in the enzyme induction. Northern blotting analysis indicated that the human IDO gene is expressed abundantly in the thymus in addition to the placenta, lung, and small intestine.

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Akihiko Kadoya: "Gene Structure of Human Indoleamine 2,3-Dioxygenase" Biochem.Biophy.Res.Commun.189. 530-536 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Melvyn P.Heyes: "Poliovirus Induces Indoleamine 2,3-Dioxygenase and Quinolinic Acid Synthesis in Mcaque Brain" FASEB J.6. 2977-2989 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Akemi Habara-Ohkubo: "Establishment of Antitoxoplasma State by Stable Expression of Mouse Indoleamine 2,3-Dioxygenase" Infect.Immun.61. 1810-1813 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Osamu Takikawa: "Synergism between IFN-γ and IL-1 α/β in Growth Inhibition of an Allografted Tumor" J.Immunol.151. 2070-2076 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Shigenobu Tone: "Assignment of the Human Indoleamine 2,3-Dioxygenase Gene to Chromosome 8 Using the Polymerase Chain Reaction" Hum.Genet.93. 201-203 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kadoya A., Tone S., Maeda H., Minatogawa Y., and Kido R.: "Gene structure of human indoleamine 2,3-dioxygenase" Biochem.Biophy.Res.Commun.189. 530-536 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Heyes M.P., Saito K., Jacobowitz D., Markey S.P., Takikawa O., and Vickers J.H.: "Poliovirus induces indoleamine 2,3-dioxygenase and quinolinic synthesis in macaque brain" FASEB J.6. 2977-2989 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Habara-Ohkubo A., Shirahata T., Takikawa O., and Yoshida R.: "Establishment of an antitoxoplasma state by stable expression of mouse indoleamine 2,3-dioxygenase" Infect.and Immun.61. 1810-1813 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takikawa O., Yasui H., Oku T., and Yoshida R.: "Synergism between IFN-gamma and IL-1alpha/beta in growth inhibition of an allografted tumor" J.Immunol.151. 2070-2076 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tone S., Kadoya A., Maeda H., Minatogawa Y., and Kido R.: "Assignment of the human indoleamine 2,3-dioxygenase gene to chromosome 8 using the polymerase chain reaction" Hum.Genet.93. 201-203 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Osamu Takikawa: "Synergism between IFN‐γ and IL‐α/β in Growth Inhibition of an Allografted Tumor" J.Immunol.151. 2070-2076 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Akemi Habara‐Ohkubo: "Establishment of Antitoxoplasma State by Stable Expression of Mouse Indoleamine 2,3‐Dioxygenase" Infect.Immun.61. 1810-1813 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Habara-Ohkubo,A: "Establishment of antitoxoplasma state by stable expression of mouse indoleamine 2,3-dioxygenase" Infect.Immun.(1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kadoya,A: "Gene structure of human indoleamine 2,3-dioxygenase" Biochem.Biophy.Res.Commun.189. 530-536 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Heyes,M.P.: "Poliovirus induces indoleamine 2,3-dioxygenase and quinolinic acid synthesis in macaque brain" FASEB J.6. 2977-2989 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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