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Role of poly ADP polymerase in transcriptional regulation by nuclear receptor

Research Project

Project/Area Number 11671083
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionShinshu University

Principal Investigator

MIYAMOTO Takahide  Shinshu Univ., Dept of Geriatrics, Lecturer, 医学部, 講師 (20192768)

Co-Investigator(Kenkyū-buntansha) ICHIKAWA Kazuo  Shinshu Univ., Dept of Geriatrics, Lecturer, 医学部, 講師 (40159835)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsNuclear receptor / Transcription / poly( ADP-ribose ) polymerase / Interaction / ADPリボースポリメラーゼ / 甲状腺ホルモン / リボシル化 / レチノイン酸 / レチノイドx受容体 / 転写仲介因子 / DNA結合 / ポリADPリボース / リガンド / 転写制御
Research Abstract

Mammalian poly( ADP-ribose ) polymerase ( PARP ) is a nuclear chromatin-associated protein with molecular mass of 114 kDa that catalyzes the transfer of ADP-ribose units from NAD+ to nuclear proteins that are located within the chromatin. We report here the identification of a novel property of PARP as a modulator of nuclear receptor signalling. PARP directly bound to the retinoid X receptors ( RXR ) and repressed the ligand-dependent transcriptional activities mediated by the heterodimers of RXR and the thyroid hormone receptor ( TR ). The interacting surface is located in the DNA binding domain of RXRa. The gel shift assay demonstrated that PARP bound to the TR/RXR heterodimers on the response element. Overexpression of the wild-type PARP selectively blocked the nuclear receptor function in the transient transfection experiments, while the enzyme defective mutant PARP did not show significant inhibition, suggesting that the essential role of poly ADP-ribosyl enzymatic activity in the gene regulation by nuclear receptors, Furthermore the PARP fused to Gal4 DNA binding domain suppressed the transcriptional activity of promoter harboring Gal4 binding site. Thus the PARP has transcriptional represser activity when recruited to the promoter. These results indicates that poly ADP-ribosylation is a negative co factor in gene transcription, regulating the member of the nuclear receptor superfamily.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Miyamoto T et al.: "The role of hinge domain heterodimerization and specific DNA recognition by nuclear receptors"Mol Cell Endocrinol. 181. 229-238 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Miyamoto T et al.: "Expression of dominant negative form of PAX4 in human insulinoma"Biochem Biophys Res Commun. 282. 34-40 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kakizawa T et al.: "Silencing mediator for retinoid and thyroid hormone recepeors interacts with oct-1 and acts as a transcriptional represcor"J Biol Chem. 276. 9720-9725 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ichikawa K et al.: "Mechanism of liver-selective thyromimeric activity of SK&FL-94901"J Endocrinol. 165. 391-397 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hara M et al.: "Thyroid hormone regulation of apoptosis induced by retinoic acid in promyeloleukemic HL-60 cells"Thyroid. 10. 1023-1034 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takada T et al.: "Quantaties analysis of DNA binding affinity and dimerization properties of wild-type and mutant thyroid honor reopter keta"Thyroid. 10. 11-18 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Miyamoto,T., et al.: "The role of hinge domain in heterodimerization and specific DNA recognition by nuclear receptor"Mol Cell Endocrinol. 181. 229-238 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Miyamoto,T., et al.: "Expression of dominant negative form of PAX4 in human insulinoma"Biochem Biophys Res Commun. 282. 34-40 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kakizawa,T., et al.: "Silencing mediator for retinoid and thyroid hormone receptors interacts with octamer transcription factor-1 and acts as a transcriptional represser"J Biol Chem. 276. 9720-5 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ichikawa,K., et al.: "Mechanism of liver-selective thyromimetic activity of SK&F L-94901 : evidence for the presence of a cell-type-specific nuclear iodothyronine transport process"J Endocrinol. 165. 391-397 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hara,M., et al.: "Thyroid hormone regulation of apoptosis induced by retinoic acid in promyeloleukemic HL-60 cells: Studies with retinoic acid receptors- and retinoid X receptors-specific ligands"Thyroid. 10. 1023-1034 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeda,T., et al.: "Quantitative analysis of DNA binding affinity and dimerization properties of wild-type and mutant thyroid hormone receptor beta1"Thyroid. 10. 11-18 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Miyamoto T, et al.: "The role of hinge domain in heterodimerization and specific DNA recognition by nuclear receptors"Mol Cell Endocrinol. 181. 229-238 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Miyamoto T, et al.: "Expression of dominant negative form of PAX4 in human insulinoma"Biochem Biophys Res Commun. 282. 34-40 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kakizawa T et al.: "Silencing mediator for netinoid and thyroid hormone receptors interacts with OCT-1 and acts as a transcriptional heprescor"J Biol Chem. 276. 9720-9725 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ichikawa K, et al.: "Mechanism of liver-selective thyromimeric actioity of SK&FL-94901"J Endocrinol. 165. 391-397 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hara M, et al.: "Thyroid hormone regulation of apoptosis induced by retinotc acid in promyelolenkemic HL-60 cells"Thyroid. 10. 1023-1034 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takeda T, et al.: "Quantative analysis of DNA binding attinity and dimerization properties of wild-type and mutant thyroid hormor receptor keta"Thyroid. 10. 11-18 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kakizawa T.Miyamoto T. et al.: "Silencing mediator for retinoid and thyroid hormone receptors interacts with Oct-1 and acts as a transcriptionl repressor"J.Biol.Chem.. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miyamoto,T.: "Inhibition of nuclear receptor signaling by poly(ADP-ribose) polymerase"19. 2644-2649 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kakizawa,T.: "Functional interaction between Oct-1 and retinoid X receptor"J Biol Chem. 274. 19103-19108 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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