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Cloning and characterization of a novel coactivator, ANT-1, for androgen receptor AF-1 domain

Research Project

Project/Area Number 14571068
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

GOTO Kiminobu  KYUSHU UNIVERSITY, University Hospital, Research Associate, 大学病院, 助手 (90284512)

Co-Investigator(Kenkyū-buntansha) YANASE Toshihiko  KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Associate Professor, 医学研究院, 助教授 (30239818)
NAWATA Hajime  KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Professor, 医学研究院, 教授 (10038820)
名和田 新  九州大学, 大学院・医学研究院, 教授 (10038200)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsandrogen receptor / transcriptional coactivator / activation function-1 / confocal microscopy / nuclear localization signal / subnuclear compartment / mammalian two-hybrid / Activation Function-1 / 分子内機能ドメイン / mammalian two-hybrid法 / 核内クラスター / GFP / AF-1 / コアクチベーター / スプライシング因子
Research Abstract

We have previously identified a novel coactivator for the activation function-1 (AF-1) domain of the androgen receptor (AR). This coactivator, named androgen receptor N-terminal domain transactivating protein-1 (ANT-1), is unique, since the ANT-1 is a component of U5 small nuclear ribonucleoparticle (snRNP), thus raising the possibility that the AR-AF-1 may be involved in the transcription-splicing coupling via ANT-1. We identified four distinguished functional domains required for ANT-1 to play a role as a unique coactivator for AR ; which were transactivating domain, AR-AF-1 binding domain, nuclear translocation signal domain, and intranuclear speckle formation domain. In the ANT-1, consisted of 941 amino acid (aa) residues, about two thirds of the molecule from 291 aa to the C-terminal end contains 19 tetratricopeptide repeat (TPR) motifs which has been speculated to play a role in protein-protein interactions. Interestingly both AR-AF-1 binding domain and the speckle formation domain of ANT-1 were assigned within this long region containing multiple TPR motifs, while transactivating domain and the nuclear translocation signal resided only in the 1 to 172 aa residues. Furthermore, the transactivating domain of ANT-1 was not specific for the AR, that is it enhanced even non-specific viral prompters. The receptor specificity of ANT-1 transactivation was simply determined by the TPR containing region. These results indicated that the ANT-1 actually contained four distinguished intramolecular functional domains, thus suggesting that the ANT-1 play a significant role in vivo.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (14 results)

All 2006 2005 2004 2003 2002 Other

All Journal Article (9 results) Publications (5 results)

  • [Journal Article] Identification of the functional domains of ANT-1, a novel coactivator of the androgen receptor2006

    • Author(s)
      Fan S, et al.
    • Journal Title

      Biochem Biophys Res Commun. 341

      Pages: 192-201

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of the functional domains of ANT-1, a novel coactivator of the androgen receptor.2006

    • Author(s)
      Fan S, et al.
    • Journal Title

      Biochem Biophys Res Commun. 341

      Pages: 192-201

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Dehydroepiandrosterone negatively regulates the p38 mitogen-activated protein kinase pathway by a novel mitogen-activated protein kinase phosphatase2005

    • Author(s)
      Ashida K. et al.
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression E-pub Feb 23

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Dehydroepiandrosterone negatively regulates the p38 mitogen-activated protein kinase pathway by a novel mitogen-activated protein kinase phosphatase.2005

    • Author(s)
      Ashida K. et al.
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - GeneStructure and Expression 1728

      Pages: 84-94

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Dehydroepiandrosterone negatively regulates the p38 mitogen-activated protein kinase pathway by a novel mitogen-activated protein kinase phosphatase2005

    • Author(s)
      Ashida K. et al.
    • Journal Title

      Biochimica et Biophysica Acta (BBA)-Gene Structure and Expression E-pub Feb 23(印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] SF-1/Ad4BP transforms primary long-term cultured bone marrow cells into ACTH-responsive steroidogenic cells.2004

    • Author(s)
      Gondo S. et al.
    • Journal Title

      Genes Cells 9

      Pages: 1239-1247

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Activation function-1 domain of androgen receptor contributes to the interaction between two distinct subnuclear compartments.2003

    • Author(s)
      Goto K.et al.
    • Journal Title

      J Steroid Biochem Mol Biol. 85

      Pages: 201-208

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Activation function-1 domain of androgen receptor contributes to the interaction between subnuclear splicing factor compartment and nuclear receptor compartment. Identification of the p102 U5 small nuclear ribonucleoprotein particle-binding protein as a coactive-ator for the receptor2002

    • Author(s)
      Zhao Y.et al.
    • Journal Title

      J Biol Chem 277

      Pages: 30031-30039

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Activation function-1 domain of androgen receptor contributes to the interaction between subnuclear splicing factor compartment and nuclear receptor compartment.2002

    • Author(s)
      Zhao Y.et al.
    • Journal Title

      J Biol Chem 277

      Pages: 30031-30039

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Kiminobu Goto et al.: "Activation function-1 domain of androgen receptor contributes to the in teraction between two distinct subnuclear compartments"The Journal of Steroid Biochemistry and Molecular Biology. 85-2. 201-208 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Zhao, Y., Goto, K., Saitoh, M., et al.: "Activation function-1 domain of androgen receptor contributes to the interaction between subnuclear splicing factor compartment and nuclear receptor compartment"J Biol Chem. 277. 30031-30039 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nawata, H., Goto, K., Morinaga, H., et al.: "Molecular mechanisms underlying the action of environmental endocrine-disrupting chemicals"Environmental Sciences. 9. 57-70 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takayanagi, R., Goto, K., Suzuki, S., et al.: "Dehydroepiandrosterone (DHEA) as a possible source for estrogen formation in bone cells : Correlation between bone mineral density and serum DHEA-sulfate concentration in postmenopausal women, and the presence of aromatase to be enhanced by 1,25-dihydroxyvitamin D3 in human osteoblasts"Mech Ageing Dev. 123. 1107-1114 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nawata, H., Yanase, T., Goto, K., et al.: "Mechanism of action of anti-aging DHEA-S and the replacement of DHEA-S"Mech Ageing Dev. 123. 1101-1106π (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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