| Project/Area Number |
11307017
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | Kyushu University |
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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)
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| 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)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| 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)
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| Keywords | Yeast 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 |
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| 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.
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