Studies on the regulation of nuclear receptor which controls the gene expression

控制基因表达的核受体调控研究

• 批准号: 01480287
• 负责人: HASHIZUME Kiyoshi
• 金额: $ 4.22万
• 依托单位: Department of Geriatrics, Shinshu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-01480287/
• 关键词: 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

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.

研究了甲状腺激素核受体修饰因子对甲状腺激素诱导的基因表达的影响。我们已经分离并纯化了高亲和力的NADPH依赖性胞质3，5，3^1-三碘-L-甲状腺原氨酸（T3）结合蛋白（CTBP）。分析了分子大小和T3结合特性。该蛋白调节T3从细胞质到核受体的转运。然而，该蛋白质不影响磷酸基-β-6 f核T3受体。另一方面，在存在于细胞核中的蛋白激酶的情况下，核甲状腺激素受体被磷酸化。蛋白激酶不刺激CTBP的磷酸化，CTBP不仅可以被甲状腺激素诱导，也可以被活性形式的维生素D3诱导，这表明CTBP是由受体c-erb A超家族群介导的信号诱导的。出生时中枢神经系统中CTBP含量较高，提示神经系统依赖甲状腺激素的发育受CTBP控制。其中一个是在1989年发现的，另一个是在1991年。后者由多肽链二聚体组成。然而，这种蛋白质的作用尚不清楚。最近我们获得了这些CTBPS的抗体。通过对这些抗体的研究，这些CTBPS的作用，特别是对甲状腺激素诱导的基因表达的调节作用，还有待进一步研究。

项目成果

Hashizume,K.,Suzuki,S.,Ichikawa,K.,Takeda,T.,& Kobayashi,M.: "Effect of active vitamin D3 on the levels of NADPH-dependent cytosolic 3,5.3'-triiodo-L-thyronine-binding protein" Biochiem.Biophys,Res.Commun.177. 388-394 (1991)

桥爪 K.、铃木 S.、市川 K.、武田 T.、

Hashizume, K., Suzuki, S., Ichikawa, K., Takeda, T.: "Purification of cytosolic 3, 5, 3^1 -triiodo-L-thyronine (T_3) -binding protein (CTBP) which regulates nuclear T_3 translocation" Biochim. Biophys. Res. Commun.174. 1084-1089 (1991)

Hashizume, K.、Suzuki, S.、Ichikawa, K.、Takeda, T.：“调节核 T_3 的胞质 3, 5, 3^1 -三碘-L-甲状腺氨酸 (T_3) 结合蛋白 (CTBP) 的纯化

Hashizume,K.,Suzuki,S.,Ichikawa,K.,& Takeda,T.: "Purification of cytosolic 3,5,3'-triiodo-L-thyronine(T_3)-binding protein(CTBP)which regulates nuclear T_3 translocation" Biochim.Biophys,Re.Commun.174. 1084-1089 (1991)

桥爪 K.、铃木 S.、市川 K.、

Hashizume,K.,Ichikawa,K.,Suzuki,S.,Takeda,T.,Yamauchi,K.,Kobayashi,M.: "Evidence for the presence of protein kinases which stimulate Phosphorylation of c-erb A protein in rat kidney nuclei" Endocrinol.Japon. 38. 205-212 (1991)

Hashizume,K.、Ichikawa,K.、Suzuki,S.、Takeda,T.、Yamauchi,K.、Kobayashi,M.：“存在刺激大鼠肾脏中 c-erb A 蛋白磷酸化的蛋白激酶的证据

Kobayashi, M., Hashizume, K., Suzuki, S., Ichikawa, K., Takeda, T.: Endocrinology. 129. 1701-1708 (1991)

小林，M.，桥爪，K.，铃木，S.，市川，K.，武田，T.：内分泌学。