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Establishment of new disease concept, nuclear receptor cofactor disease

Research Project

Project/Area Number 11307017
Research Category

Grant-in-Aid for Scientific Research (A)

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

Principal Investigator

NAWATA Hajime  Graduate School of Medical Sciences, Medicine and Bioregulatory Science, Kyushu University, Professor, 大学院・医学研究院, 教授 (10038820)

Co-Investigator(Kenkyū-buntansha) GOTO Kiminobu  Graduate School of Medical Sciences, Medicine and Bioregulatory Science, Kyushu University, Assistant Professor, 大学院・医学研究院, 助手 (90284512)
YANASE Toshihiko  Graduate School of Medical Sciences, Medicine and Bioregulatory Science, Kyushu University, Associate Professor, 大学院・医学研究院, 助教授 (30239818)
TAKAYANAGI Ryoichi  Graduate School of Medical Sciences, Medicine and Bioregulatory Science, Kyushu University, Professor, 大学院・医学研究院, 教授 (30154917)
NOMURA Masatoshi  Graduate School of Medical Sciences, Medicine and Bioregulatory Science, Kyushu University, Assistant Professor, 大学院・医学研究院, 助手 (30315080)
OKABE Taijiro  Graduate School of Medical Sciences, Medicine and Bioregulatory Science, Kyushu University, Assistant Professor, 医学部・附属病院, 助手 (40264030)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥32,600,000 (Direct Cost: ¥30,500,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2001: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2000: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1999: ¥16,500,000 (Direct Cost: ¥16,500,000)
KeywordsYeast two-hybrid assay / AR AF-1 / GST pull-down / cDNA cloning / TPR / アンドロゲン / 共役因子 / 睾丸性女性化症 / 受容体 / 不応症 / 転写 / ステロイドホルモン
Research Abstract

During 1998 through 1999, we identified the 90kDa protein that is specifically disrupted in the patient with androgen receptor coactivator disease, using a glutathione-S-transferase pull-down experiment.
To isolate this protein, in 2001, we performed a yeast two-hybrid screening using the androgen receptor AF-1 sequence as a bait. We isolated a protein, consisted of 941 a.a. residues, the amino acid sequence of which had previously been reported. This protein contains 19 TPR (tetratrico peptide repeat) in the molecule, leading to the tentative naming "TPR protein". The overexpression of this TPR protein in the cultured cells enhanced the androgen receptor-dependent transactivation function by three to five fold, and the protein was proved to bind to AF-1 sequence in the living cells, whereas this protein did not enhance the estrogen receptor-dependent transactivations.
To further investigate whether or not this protein is mutated in the cells from the patient, we are currently determining the nucleotide sequence of the TPR protein cDNA, using 12 primers, from patient cells. Furthermore, we also are searching the sequences the expressions of which are down-regulated in the patient's cells, when compared with normal subjects, with the aid of DNA chip method.

Report

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

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Saitoh M, Yanase T, Morinaga H, Tanabe M, Mu YM, Nishi Y, Nomura M, Okabe T, Goto K, Tkayanagi R, Nawata H.: "Tributyltin or Triphenyltin Inhibits Aromatase Activity in the Human Granulosa-like Tumor Cell Line KGN"Biochem Biophys Res Commun. 289. 198-204 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nishi Y, Yanase T, Mu Y, Oba K, Ichino I, Saito M, Nomura M, Mukasa C, Okabe T, Goto K., Takayanagi R, Kashimura Y, Haji M, Nawata H.: "Establishment and characterization of a steroidogenic human granulosa-like tumor cell line, KGN that expresses functional FSH receptor"Endocrinology. 142. 437-445 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yanase T, Mu YM, Nishi Y, Goto K, Nomura M, Okabe T, Tkayanagi R, Nawata H.: "Regulation of aromatase by nuclear receptors"J Steroid Biochem Mol Biol.. 79. 187-192 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mu Y, Yanase T, Nishi Y, Saito M, Nomura M, Mukasa C, Okabe T, Goto K, Nawata H.: "Saturated free fatty acids, palmitic acid and stearic acid induces apoptosis of human granulosa cells"Endocrinology. 142. 3590-3597 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tomura A, Goto K, Morinaga H, Nomura M., Okabe T, Yanase T, Takayanagi R, Nawata H.: "The subnuclear three-dimensional image analysis of androgen receptor fused to fluorescence protein"J Biol Chem. 276. 28395-28401 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mu YM, Yanase T, Nishi Y, Takayaagi R, Goto K, Nawata H.: "Nuclear receptor constituted by PPARg : RXR heterodimers inhibits the expression of cytochrome p450 in human granulosa cells"Mol Cell Endocrinol. 181. 239-248 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Saitoh M, Yanase T, Morinaga H, Tanabe M, Mu YM, Nishi Y, Nomura M, Okabe T, Goto K, Takayanagi R, Nawata H: "Tributyltin or Triphenyltin Inhibits Aromatase Activity in the Human Granulosa-like Tumor Cell Line KGN"Biochem Biophys Res Commun.. 289. 198-204 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nishi Y, Yanase T, Mu Y, Oba K, Ichino I, Saito M, Nomura M, Mukasa C, Okabe T, Goto K, Takayanagi R, Kashimura Y, Haji M, Nawata H: "Establishment and characterization of a steroidogenic human granulosa-like tumor cell line, KGN that expresses functional FSH receptor"Endocrinology. 142. 437-445 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yanase T, Mu YM, Nishi Y, Goto K, Nomura M, Oka be T, Takayanagi R, Nawata H: "Regulation of aromatase by nuclear receptors"J Steroid Biochem Mol Biol. 79. 187-192 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mu Y, Yanase T, Nishi Y, Saito M, Nomura M, Mukasa C, Okabe T, Goto K, Nawata H: "Saturated free fatty acids, palmitic acid and stearic acid induces apoptosis of human granulosa cells"Endocrinology. 142. 3590-3597 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tomura A, Goto K, Morinaga H, Nomura M, Okabe T, Yanase T, Takayanagi R, Nawata H: "The subnuclear three-dimensional image analysis of androgen receptor fused to fluorescence protein"J Biol Chem. 276. 28395-401 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mu YM, Yanase T, Nishi Y, Takayanagi R, Goto K, Nawata H: "Nuclear receptor constituted by PPARg : RXR heterodimers inhibits the expression of cytochrome p450 in human granulosa cells"Mol Cell Endocrinol. 181. 239-248 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Saitoh M, Yanase T, Morinaga H, Tanabe M, Mu YM, Nishi Y, Nomura M, Okabe T, Goto K, Tkayanagi R, Nawata H.: "Tributyltin or Triphenyltin Inhibits Aromatase Activity in the human Granulosa-like Tumor Cell Line KGN"Biochem Biophys Res Commun.. 289. 198-204 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nishi Y, Yanase T, Mu Y, Oba K, Ichino I, Saito M, Nomura M, Mukasa C, Okabe T, Goto K., Takayanagi R, Kashimura Y, Haji M, Nawata H.: "Establishment and characterization of a steroidogenic human granulosa-like tumor cell line, KGN that expresses functional FSH receptor"Endocrinology. 142. 437-445 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yanase T, Mu YM, Nishi Y, Goto K, Nomura M, Okabe T, Tkayanagi R, Nawata H.: "Regulation of aromatase by nuclear receptors"J Steroid Biochem Mol Biol.. 79. 187-192 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Mu Y, Yanase T, Nishi Y, Saito M, Nomura M, Mukasa C, Okabe T, Goto K, Nawata H.: "Saturated free fatty acids, palmitic acid and stearic acid induces apoptosis of human granulosa cells"Endocrinology. 142. 3590-3597 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tomura A, Goto K, Morinaga H, Nomura M, Okabe T, Yanase T, Takayanagi R, Nawata H.: "The subnuclear three-dimensional image analysis of androgen receptor fused to fluorescence protein"J Biol Chem. 276. 28395-28401 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Mu YM, Yanase T, Nishi Y, Takayaagi R, Goto K, Nawata H.: "Nuclear receptor constituted by PPARg : RXR heterodimers inhibits the expression of cytochrome p450 in human granulosa cells"Mol Cell Endocrinol. 181. 239-248 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Adachi M. et al: "Androgen Insensitivity Syndrome as a Possible Coactivator Disease"The New England Journal of Medicine. 343・12. 856-862 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Oba K. et al: "Transcriptional Regulation of the Human FTZ-F1 Gene Encoding Ad4BP/SF-1"Journal of Biochemistry. 128・3. 517-528 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yi-Ming Mu et al: "A Nuclear Receptor System Constituted by RAR and RXR Induces Aromatase Activity in MCF-7 Human Breast Cancer Cells"Molecular and Cellular Endocrinology. 166. 137-145 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 名和田新 他: "ホルモンと臨床 転写共役因子による転写制御のメカニズム(48・増刊号)"36-38 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 高柳涼一 他: "ホルモンと臨床 AR活性の細胞性御因子:ARの活性発現に必須のAF-1特異的共役因子の存在を示唆するアンドロゲン不応症(48・増刊号)"44-49 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 岡部泰二郎 他: "組織培養工学 ステロイドホルモンレセプターと疾患(26・13)"507-512 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Okabe T.: "Nur77,a member of the steroid receptor superfamily,antagonizes negative feedback of ACTH synthesis and secretion by glucocorticoid in pituitary corticotrope cells"J,Endocrionol.. 156. 169-175 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Netori S.: "Chromogranin B(secretogranin I),a neurooendocrine-regulated secretory protein,is sorted to exocrins secretory granules in transgenic mice"The EMBO J,. 17. 3277-3289 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ikuyama S.: "Expression of an orphan nuclear receptor DAX-1 in human pituitary adenomas"Clin,Endcrinol.. 48. 647-654 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Mu,Y-M.: "Low level of glucocorticoid receptor messenger ribonucleic acid in pituitary adenomas manifesting Cushing's disease with resistance to a high dose-dexamethasone suppression test"Clin,Endocrinol.. 49. 301-306 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hamaguchi K.: "Novel germline mutations ot the MEN1 gene in Japanese patients with multiple endocrine neoplasia type"J.Hum,Genet. 44. 43-47 (1999)

    • Related Report
      1999 Annual Research Report

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

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