| Project/Area Number |
01480287
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Department of Geriatrics, Shinshu University School of Medicine |
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Principal Investigator |
HASHIZUME Kiyoshi Department of Geriatrics, Shinshu University School of Medicine Associate Professor, 医学部附属病院・老年科, 講師 (60092889)
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| Co-Investigator(Kenkyū-buntansha) |
市川 和夫 信州大学, 医学部附属病院老年科, 助手 (40159835)
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| Project Period (FY) |
1989 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1991: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1990: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1989: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Keywords | Thyroid hormone nuclear receptor / Cytosolic T3-binding protein (CTBP) / Nuclear protein kinase / Gene expression / 核リン酸化酵素 / 甲状腺ホルモン結合蛋白 / 甲状腺ホルモン受容体 / 転写開始シグナル / 細胞質甲状腺ホルモン結合物質 / ホルモン情報 / 情報伝達因子 / Acceptor蛋白 / NADPH / NADP |
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| Research Abstract |
Effects of factors which modify the thyroid hormone nuclear receptors on the gene expression induced by the thyroid hormone were investigated. We have isolated and purified the high affinity NADPH-dependent cytosolic 3, 5, 3^1-triiodo-L-thyronine(T3)-binding protein(CTBP). The molecular size and T3 binding characteristics were analyzed. The protein regulates the T3 tranlocation, from cytoplasm to nuclear receptor. However, the protein did not affect the phosphokyli-flon- 6f nuclear T3 receptor. On the other hand, the nuclear thyroid hormone receptor was phosphorylated in the presence of protein kinase which presents in nuclei. The protein kinase did not stimulate the phosphorylation of CTBP.
The CTBP could be induced not only by thyroid hormone but also active form of vitamin D3, which indicates that the CTBP is induced by a signal which is mediated by receptors, c-erb A superfamily group. The content of CTBP in central nervous system was high at the time of birth, suggesting that the thyroid hormone-dependent development of nervous system is controlled by CTBP.
During studies on CTBP, we isolated two different CTBPS. One of them was found in 1989, and the other was in 1991. The latter was composed of dimer of polypeptide chain. However, the role of this protein was not known. Recently we obtained the antibodies to these CTBPS. By studying with these antibodies, the roles of these CTBPS, especially regulation of throid hormone-induced gene expression, niay become to be clear.
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