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REGULATION OF HYPOXIA RESPONSE GENES BY NEW TRANSCRIPTION FACTOR

Research Project

Project/Area Number 13680728
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionNATIONAL CANCER CENTER RESEARCH INSTITUTE

Principal Investigator

OGURA Tsutomu  NATIONAL CANCER CENTER RESEARCH INSTITUTE EAST, INVESTIFATIVE TREATMENT DIVISION, SECTION HEAD, がん治療開発部, 室長 (80211134)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordshypoxia / nitric oxiae / HAS / gene regulation / HIF-PH / HIF-PH / 転写因子 / 発現制御
Research Abstract

The hypoxia response of a living body regulated by the activation of hypoxia inducible factor (I-HF-1), and its binding to hypoxia response element (I-IRE) which exists in the transcriptionally regulatory region of various hypoxia oxygen response genes. We found that nitric oxide (NO) which is generated in the living body in addition to hypoxic response up-regulate vascular endothelial growth factor (VEGF) gene expression by the same mechanism as hypoxia. Furthermore, we clarified that new transcriptional factor bind to HIF-1 ancillary arrangement (HAS) which is located in the lower stream of I-IRE existed in promoter region of the hypoxia response genes by hypoxia or NO. The binding proteins had the molecular weight of 100Kd and 45Kd. By molecular cloning of HAS binding protein from HeLa cell cDNA library, we identified two clones which are nuclease sensitive element binding protein and protein inhibitor of activated STAT X. Recently, it has shown that HIF-1 proryl hydroxylase (I-HF-PH) regulated HIF-1 degradation under normoxic condition. Under hypoxic condition, HIF-PH activity was inhibited because oxygen is a cofactor of HIF-PH reaction. It is also clear that the iron ion is required as cofactor of the enzyme reaction. We clarified that NO inhibits enzymatic reaction of HTF-PH by forming a nitrosyl iron complex. In this study, we demonstrated that different mechanism of the activation of HIF-1 by low oxygen and NO.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Imamura, K., Ogura, T.et al.: "Cell cycle regulation via p53 phosphorylation by 5'-AMP activated protein kinase activator, 5-Aminoimidazaole^4-Carboxamide-1-b-D-Ribofuranoside (AICAR), in a human hepatocellular carcinoma cell line."Biochem.Biophys.Res.Commun.. 28. 562-567 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takamochi, K., Ogura, T.et al.: "Loss of heterozygosity on chromosomes 9q and 16p in atypical adenomatous hyperplasia concomitant with adenocarcinoma of the lung."The American J.Pathol.. 159. 1941-1948 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kimura, H., Weisz, A., Ogura, T.et al.: "Identification of hypoxia-inducible factor-1 (HIF-1) ancillary sequence and its function in vascular endotherial growth factor gene induction by hypoxia and nitric oxide."Journal of Biological Chemistry. 36. 32791-32798 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawasaki, H., Ogura, T.et al.: "P53 gene alteration in atypical epithelial lesions and carcinoma in patients with idiopathic pulmonary fibrosis."Human Pthol.. 32. 1043-1049 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kimura, T., Ogura, T.et al.: "Effect of nitric oxide donors on vascular endothelial growth factor gene induction"Biochem.Biophys.Res.Commun.. 296. 976-982 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kato, K., Ogura, T.et al.: "Critical roles of AMP-activated kinase in constitutive tolerance of cells to nutrient deprivation and tumor formation"Oncogene. 21. 6082-6090 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Esumi, H., Ogura, T.et al.: "Hypoxia and nitric oxide treatment confer tolerance to glucose starvation in a 5'-AMP-activated kinase-dependent manner"Journal of Biological Chemistry. 36. 32791-32798 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishii, Y., Ogura, T.et al.: "Induction of matrix metalloproteinases gene transcription by nitric oxide and mechanisms of MMP-1 gene induction in human melanoma cell lines"International Journal of Cancer. 103. 6082-6090 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suzuki, A., Ogura, T.et al.: "Identification of a novel protein kinase mediating Akt survival signaling to ATM"Journal of Biological Chemistry. 278. 48-53 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suzuki, A., Ogura, T.et al.: "Identification of a novel protein kinase mediating Akt survival signaling to ATM"Journal of Biological Chemistry. 278. 48-53 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishii, Y., Ogura, T.et al.: "Induction of matrix metalloproteinases gene transcription by nitric oxide and mechanisms of MMP-1 gene induction in human melanoma cell lines"International Journal of Cancer. 103. 6082-6090 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Esumi, H., Ogura, T.et al.: "Hypoxia and nitric oxide treatment confer tolerance to glucose starvation in a 5'-AMP-activated kinase-dependent manner"Journal of Biological Chemistry. 36. 32791-32798 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kato, K., Ogura, T.et al.: "Critical roles of AMP-activated kinase in constitutive tolerance of cells to nutrient deprivation and tumor formation"Oncogene. 21. 6082-6090 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kimura, T., Ogura, T.et al.: "Effect of nitric oxide donors on vascular endothelial growth factor gene induction"Biochemical Biophysical Research Communications. 296. 976-982 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Imamura K., Ogura T., et al.: "Cell Cycle Regulation via p53 Phosphorylation by a 5'-AMP Activated Protein Kinase Activator, 5-Aminoimidazole-4-Carboxamide-1-beta-d-Ribofuranoside, in a Human Hepatocellular Carcinoma Cell Line"Biochem. Biophys. Res. Commun.. 28. 562-567 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takamochi K., Ogura T., et al.: "Loss of heterozygosity on chromosomes 9q and 16p in atypical adenomatous hyperplasia concomitant with adenocarcinoma of the lung"The American J. Pathol.. 159. 1941-1948 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kimura H, Weisz A, Ogura T., ei al.: "Identification of hypoxia-inducible factor 1(HIF-1) ancillary sequence and its function in vascular endothelial growth factor gene induction by hypoxia and nitric oxide"J Biol Chem.. 276. 2292-2298 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawasaki H, Ogura T., et al.: "p53 gene alteration in atypical epithelial lesions and carcinoma in patients with idiopathic pulmonary fibrosis"Human Pathol.. 32. 1043-1049 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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