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2005 Fiscal Year Final Research Report Summary

Time and spacial analyses for mechanisms of intracellular traffic and localization of nuclear receptors using imaging analyses including FRET

Research Project

Project/Area Number 16590909
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

KAWATE Hisaya  Kyushu University, Graduate School of Medical Sciences, Research Associate, 大学院・医学研究院, 助手 (20336027)

Co-Investigator(Kenkyū-buntansha) TAKAYANAGI Ryoichi  Kyushu University, Graduate School of Medical Sciences, Professor, 大学院・医学研究院, 教授 (30154917)
Project Period (FY) 2004 – 2005
KeywordsNuclear Receptor / GFP / Steroid hormone / Transcriptional regulation / Transcriptional cofactor / Confocal laser microscopy / Hormone
Research Abstract

I. Analyses of intracellular dynamics of mutant androgen receptors (AR) derived from two androgen insensitivity syndrome (AIS) patients.
Intracellular dynamics of two different AR mutants (AR-C579F, AR-F582Y) derived from AIS patients were analysed using GFP-fused mutant ARs. The wild-type AR was ligand-dependently translocated into the nucleus where it formed fine subnuclear foci. Surprisingly, after the addition of dihydrotestosterone (DHT), the two mutant ARs initially formed large cytoplasmic dots, many of which were found to be close to mitochondria by electron microscopy. Subsequently, a proportion of the ligand-bound mutant ARs gradually entered the nucleus to form a smaller number of larger dots compared with the wild-type AR. Fluorescence recovery after photobleaching (FRAP) analysis revealed that the intranuclear mobilities of the mutant ARs were decreased compared with that of the wild-type AR. These results suggest that the abnormal translocation, localization and mobility o … More f the mutant ARs may be the cause of AIS in these subjects.
II. Analyses of transcriptional repression mechanisms by novel corepressors, TZF and Tob
We showed that testicular zinc finger protein, TZF, was a novel corepressor for AR. TZF was ligand-dependently colocalized with AR and interacted with the N-terminus of AR. A central portion (amino acids 512-663) of TZF, TZF(512-663), is responsible for both binding to AR and repressing the transactivation. TZF recruited endogenous histone deacetylase 2 (HDAC2) and formed a complex with agonist-bound AR. Imaging analyses showed that TZF and TZF(512-663) were recruited by AR and simultaneously impaired distinct AR foci formation. Quantification of the foci number using a three-dimensional imaging method revealed that the number of intranuclear AR foci was related to its transactivation activity. Moreover, increased levels of TZF dissociated a coactivator, TIF2, from the AR foci and vice versa. These results indicate that the ligand-dependent transactivation function of AR is quantitatively related to its intranuclear foci formation, and suggest that corepressors, such as TZF, act on these intranuclear events competitively with coactivators.
We also found that Tob, which was regarded as a negative regulator of osteoblast function, repressed transactivation function of AR, ER and GR. Less

  • Research Products

    (19 results)

All 2006 2005 2004

All Journal Article (17 results) Book (2 results)

  • [Journal Article] Opposite effects of alternative TZF spliced variants on androgen receptor.2006

    • Author(s)
      Tao R-H. et al.
    • Journal Title

      Biochemical and Biophysical Research Communication 341・2

      Pages: 515-521

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Testicular zinc finger protein recruits histone deacetylase 2 and suppresses the transactivation function and intranuclear foci formation of agonist-bound androgen receptor competitively with TIF22006

    • Author(s)
      Tao R-H. et al.
    • Journal Title

      Molecular and Cellular Endocrinology 247・1-2

      Pages: 150-165

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Opposite effects of alternative TZF spliced variants on androgen receptor2006

    • Author(s)
      Tao R-H. et al.
    • Journal Title

      Biochem Biophys Res Commun 341

      Pages: 515-521

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Testicular zinc finger protein recruits histone deacetylase 2 and suppresses the transactivation function and intranuclear foci formation of agonist-bound androgen receptor competitively with TIF22006

    • Author(s)
      Tao R-H. et al.
    • Journal Title

      Molecular and Cellular Endocrinology 240

      Pages: 150-165

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Tob proteins suppress steroid hormone receptor-mediated transcriptional activation.2005

    • Author(s)
      Kawate H. et al.
    • Journal Title

      Molecular and Cellular Endocrinology 230・1-2

      Pages: 77-86

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts2005

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

      Biochemical and Biophysical Research Communication 329・1

      Pages: 177-181

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A zinc finger protein TZF is a novel corepressor of androgen receptor2005

    • Author(s)
      Ishizuka M. et al.
    • Journal Title

      Biochemical and Biophysical Research Communication 331・4

      Pages: 1025-1031

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Impaired nuclear translocation,nuclear matrix targeting,and intranuclear mobility of mutant androgen receptors carrying amino acid substitutions in the deoxyribonucleic acid-binding domain derived from androgen insensitivity syndrome patients.2005

    • Author(s)
      Kawate H. et al.
    • Journal Title

      Journal of Clinical Endocrinology and Metabolism 90・11

      Pages: 6162-6169

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Tob proteins suppress steroid hormone receptor-mediated transcriptional activation.2005

    • Author(s)
      Kawate H. et al.
    • Journal Title

      Molecular and Cellular Endocrinology 230

      Pages: 77-86

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts2005

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

      Biochem Biophys Res Commun 329

      Pages: 177-181

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A zinc finger protein TZF is a novel corepressor of androgen receptor2005

    • Author(s)
      Ishizuka M. et al.
    • Journal Title

      Biochem Biophys Res Commun 331

      Pages: 1025-1031

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Impaired nuclear translocation, nuclear matrix targeting, and intranuclear mobility of mutant androgen receptors carrying amino acid substitutions in the deoxyribonucleic acid-binding domain derived from androgen insensitivity syndrome patients.2005

    • Author(s)
      Kawate H. et al.
    • Journal Title

      J Clin Endocrinol Metab 90

      Pages: 6162-6169

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Protein kinase A potentiates adrenal 4 binding protein/steroidogenic factor 1 transactivation by reintegrating the subcellular dynamic interactions of the nuclear receptor with its cofactors,general control nonderepressed-5/transformation domain-associated protein,and suppressor,dosage-sensitive sex reversal-1 : a laser confocal imaging study in living KGN cells.2004

    • Author(s)
      Fan WQ et al.
    • Journal Title

      Molecular Endocrinology 18・1

      Pages: 127-141

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Glucocorticoid enhances the expression of dickkopf-1 in human osteoblasts : novel mechanism of glucocorticoid-induced osteoporosis2004

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

      Biochemical and Biophysical Research Communication 318・1

      Pages: 259-264

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] DNA結合ドメインの変異により、アンドロゲン受容体の核移行障害、核内局在障害および核内でのmovilityの低下を認めたアンドロゲン不応症の2例2004

    • Author(s)
      河手 久弥 他
    • Journal Title

      ホルモンと臨床「内分泌 興味ある症例 第45集」 52・増刊

      Pages: 134-139

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Protein kinase A potentiates adrenal 4 binding protein/steroidogenic factor 1 transactivation by reintegrating the subcellular dynamic interactions of the nuclear receptor with its cofactors, general control nonderepressed-5/ transformation domain-associated protein, and suppressor, dosage-sensitive sex reversal-1 : a laser confocal imaging study in living KGN cells.2004

    • Author(s)
      Fan WQ et al.
    • Journal Title

      Molecular Endocrinology 18

      Pages: 127-141

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Glucocorticoid enhances the expression of dickkopf-1 in human osteoblasts : novel mechanism of glucocorticoid-induced osteoporosis2004

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

      Biochem Biophys Res Commun 318

      Pages: 259-264

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] 健康管理と臨床検査-早期診断を目指して- 第2章 生活習慣病および関連疾患-早期診断のポイントと問題点- 13.骨粗鬆症、変形性膝関節症2005

    • Author(s)
      河手 久弥, 高柳 涼一
    • Total Pages
      255
    • Publisher
      宇宙堂八木書店
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 日常生活に活かす老年病ガイドブック2 高齢者の薬の使い方 抗加齢療法とは2005

    • Author(s)
      河手 久弥, 高柳 涼一
    • Total Pages
      286
    • Publisher
      メジカルビュー社
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2007-12-13  

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