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2001 Fiscal Year Final Research Report Summary

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
KeywordsYeast two-hybrid assay / AR AF-1 / GST pull-down / cDNA cloning / TPR
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.

  • Research Products

    (12 results)

All Other

All Publications (12 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 2003-09-17  

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