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Molecular mechanism of nuclear translocation and intracellular cross talk of AhR

Research Project

Project/Area Number 11839025
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research InstitutionTokyo Women's Medical University

Principal Investigator

TSUKAHARA Fujiko  Tokyo Women's Medical University, School of Medicine, Instructor, 医学部, 助手 (40119996)

Co-Investigator(Kenkyū-buntansha) YOSHIOKA Toshimasa  Tokyo Women's Medical University, School of Medicine, Associate professor, 医学部, 助教授 (60146438)
MURAKI Takamura  Tokyo Women's Medical University, School of Medicine, Professor, 医学部, 教授 (50051446)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordsaryl hydrocarbon receptor (dioxine receptor) / nuclear import / nuclear export / molecular chaperone / cochaperone / heat shock protein 90 / cross talk / green fluorescent protein
Research Abstract

The aryl hydrocarbon receptor (AhR) mediates signal transduction elicited by environmental toxin, e. g. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). AhR binds heat shock protein 90 (hsp90) in the cytosol. Upon ligand binding, AhR translocates into nucleus to activate the transcription of target genes and exhibits toxic effects of environmental toxins. Thus, nucleocytoplasmic shuttling of AhR is an important step in the regulation of AhR action. In the present study, we analyzed molecular mechanism of nucleocytoplasmic shuttling and intracellular cross talk of AhR using the cells expressing a fusion protein of green fluorescent protein and AhR.
1. Hsp90 inhibitors significantly inhibited ligand-induced transcriptional activation of AhR.However, Hsp90 inhibitors paradoxically caused a transient nuclear translocation of unliganded AhR.These unliganded nuclear AhR redistributes to cytoplasm without activating gene transcription. The nuclear trafficking of AhR may provoke rapid degradation of the receptor by proteasomes.
2. The effect of molecular chaperones and cochapeornes on the nucleocytoplasmic shuttling of AhR was studied. The overexpression of hsp90, hsc70, p60, hsp40 or p23 did not affect ligand-induced nuclear translocation of AhR.However, the nuclear export of AhR was attenuated by overexpression of nuclear hsp90, hsc70, p60 and hsp40. Thus, nuclear hsp90, hsc70, p60 and hsp40 appear to regulate the nuclear retention of AhR.AhR may cross talk with other nuclear receptors or signal transduction molecules via these molecular chaperones and cochaperones.

Report

(2 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] Fujiko Tsukahara: "Molecular and functional characterization of HSC54, a novel variant of human heat-shock cognate protein 70."Molecular Pharmacology. 58. 1257-1263 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 吉岡俊正: "融合遺伝子発現系によるタンパク質可視化技術の分子薬理学的応用"日本薬理学雑誌. 116. 36-42 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujiko Tsukahara: "Effects of HSP90 inhibitors, geldanamycin and radicicol, on the nuclear translocation of dioxin receptor."7th World Conference on Clinical Pharmacology and Therapeutics. Abstracts. 285 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujiko Tsukahara: "Heat shock protein 90 inhibitors induce the transient nuclear translocation of dioxin receptor (AhR)."Japanese Journal of Pharmacology. 85,Suppl.(In press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Katsuya Tago: "Role of nuclear heat shock protein 90 (HSP90) on glucocorticoid-mediated nucleocytoplasmic shuttling and transcription of glucocorticoid receptor."Japanese Journal of Pharmacology. 85,Suppl.(In press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujiko Tsukahara: "Nitric oxide (NO) modulates nucleocytoplasmic shuttling of glucocorticoid receptor."Japanese Journal of Pharmacology. 82,Suppl.. 120 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujiko Tsukahara: "Modulation of nucleocytoplasmic trafficking of glucocorticoid receptor by nitric oxide."10th Biennial of the International Society for Free Radical Research. Abstracts. 137 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Katsuya Tago: "Pharmacological evaluation of HSP90-dependent mechanism for nucleocytoplasmic shuttling of glucocorticoid receptor."Japanese Journal of Pharmacology. 82,Suppl.. 156P (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toshimasa Yoshioka: "Characterization of the antioxidant property of human heat shock cognate protein 70(HSC70)."10th Biennial of the International Society for Free Radical Research. Abstracts. 156 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toshimasa Yoshioka: "Anti-NO action of carvedilol in cell-free system and in vascular endothelial cells."British Journal of Pharmacology. 129. 1530-1535 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kazuyuki Mizushima: "A novel G-protein-coupled receptor gene expressed in striatum."Genomics. 69. 314-321 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Dong-Kug Choi: "Developmentally-regulated expression of mNapor encoding an apotosis-induced ELAV-type RNA binding protein."Gene. 237. 135-142 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujiko Tsukahara, Toshimasa Yoshioka, Takamura Muraki: "Molecular and functional characterization of HSC54, a novel variant of human heat-shock cognate protein 70."Molecular Pharmacology. 58. 1257-1263 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujiko Tsukahara, Toshimasa Yoshioka: "An application of fusion fluorescent proteins in the pharmacological study of intracellular protein trafficking."Folia Pharmacologica Japonica. 116. 36-42 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujiko Tsukahara, Toshimasa Yoshioka, Katsuya Tago, Ikuko Urakawa, Takamura Muraki: "Effects of HSP90 inhibitors, geldanamycin and radicicol, on the nuclear translocation of dioxin receptor."7th World Conference on Clinical Pharmacology and Therapeutics. Abstracts. 285 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujiko Tsukahara, Toshimasa Yoshioka, Katsuya Tago, Michiko Iwabuchi, Ikuko Urakawa, Takamura Muraki: "Heat shock protein 90 inhibitors induce the transient nuclear translocation of dioxin receptor (AhR)."Japanese Journal of Pharmacology 85, Suppl. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Katsuya Tago, Fujiko Tsukahara, Toshimasa Yoshioka, Takamura Muraki: "Role of nuclear heat shock protein 90 (HSP90) on glucocorticoid-mediated nucleocytoplasmic shuttling and transcription of glucocorticoid receptor."Japanese Journal of Pharmacology 85, Suppl. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujiko Tsukahara, Toshimasa Yoshioka, Katsuya Tago, Ikuko Urakawa, Takamura Muraki: "Nitric oxide (NO) modulates nucleocytoplasmic shuttling of glucocorticoid receptor."Japanese Jouranal of Pharmacology 82, Suppl. 120 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujiko Tsukahara, Toshimasa Yoshioka, Katsuya Tago, Ikuko Urakawa, Takamura Muraki: "Modulation of nucleocytoplasmic trafficking of glucocorticoid receptor by nitric oxide."10th Biennial of the International Society for Free Radical Research. Abstracts. 137 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Katsuya Tago, Toshimasa Yoshioka, Fujiko Tsukahara, Takamura Muraki: "Pharmacological evaluation of HSP90-dependent mechanism for nucleocytoplasmic shuttling of glucocorticoid receptor."Japanese Jouranal of Pharmacology. 82, Suppl. 156 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toshimasa Yoshioka, Noriko Iwamoto, Fujiko Tsukahara, Kaoru Irie, Ikuko Urakawa, Takamura Muraki: "Anti-NO action of carvedilol in cell-free system and in vascular endothelial cells."British Journal of Pharmacology. 129. 1530-1535 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toshimasa Yoshioka, Fujiko Tsukahara, Ikuko Urakawa, Noriko Iwamoto, Takamura Muraki: "Characterization of the antioxidant property of human heat shock cognate protein 70 (HSC70)."10th Biennial of the International Society for Free Radical Research. Abstract. 156 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kazuyuki Mizushima, Yasuhide Miyamoto, Fujiko Tsukahara, Yoshiyuki Sakaki, Takashi Ito: "A novel G-protein-coupled receptor gene expressed in striatum."Genomics. 69. 314-321 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Dong-Kug Choi, Takashi Ito, Fujiko Tsukahara, Momoki Hirai, Yoshiyuki Sakaki: "Developmentally-regulated expression of mNapor encoding an apotosis-induced ELAV-type RNA binding protein."Gene. 237. 135-142 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujiko Tsukahara: "Molecular and functional characterization of HSC54, a novel variant of human heat-shock cognate protein 70."Molecular Pharmacology. 58. 1257-1263 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 吉岡俊正: "融合遺伝子発現系によるタンパク質可視化技術の分子薬理学的応用"日本薬理学雑誌. 116. 36-42 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujiko Tsukahara: "Effects of HSP90 inhibitors, geldanamycin and radicicol, on the nuclear translocation of dioxin receptor."7th World Conference on Clinical Pharmacology and Therapeutics. Abstracts. 285 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujiko Tsukahara: "Heat shock protein 90 inhibitors induce the transient nuclear translocation of dioxin receptor(AhR)."Japanese Journal of Pharmacology. 85,Suppl.(In press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Katsuya Tago: "Role of nuclear heat shock protein 90(HSP90)on glucocorticoid-mediated nucleocytoplasmic shuttling and transcription of glucocorticoid receptor."Japanese Journal of Pharmacology. 85,Suppl.(In press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujiko Tsukahara: "Nitric oxide(NO)modulates nucleocytoplasmic shuttling of glucocorticoid receptor."Japanese Journal of Pharmacology. 82,Suppl.. 120 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujiko Tsukahara: "Modulation of nucleocytoplasmic trafficking of glucocorticoid receptor by nitric oxide."10th Biennial of the International Society for Free Radical Research. Abstracts. 137 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Katsuya Tago: "Pharmacological evaluation of HSP90-dependent mechanism for nucleocytoplasmic shuttling of glucocorticoid receptor."Japanese Journal of Pharmacology. 82,Suppl.. 156P (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Toshimasa Toshioka: "Characterization of the antioxidant property of human heat shock cognate protein 70(HSC70)."10th Biennial of the International Society for Free Radical Research. Abstracts. 156 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Toshimasa Yoshioka: "Anti-NO action of carvedilol in cell-free system and in vascularendothelial cells."British Journal of Pharmacology. 129. 1530-1535 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kazuyuki Mizushima: "A novel G-protein-coupled receptor gene expressed in striatum."Genomics. 69. 314-321 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Dong-Kug Choi: "Developmentally-regulated expression of mNapor encoding an apotosis-induced ELAV-type RNA binding protein."Gene. 237. 135-142 (1999)

    • Related Report
      2000 Annual Research Report

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

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