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

研究了甲状腺激素核受体修饰因子对甲状腺激素诱导基因表达的影响。我们分离纯化了高亲和力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）。分析了其分子大小和T3结合特性。该蛋白调节T3转运，从细胞质到核受体。然而，该蛋白不影响磷酸基锂- 6f核T3受体。另一方面，核甲状腺激素受体在蛋白激酶的存在下被磷酸化。蛋白激酶不刺激CTBP的磷酸化。甲状腺激素和活性维生素D3均可诱导CTBP，表明CTBP是由c- erbb a超家族受体介导的信号诱导的。出生时中枢神经系统CTBP含量较高，提示神经系统甲状腺激素依赖性发育受CTBP控制。在CTBP的研究中，我们分离了两种不同的CTBP。其中一个是1989年发现的，另一个是1991年发现的。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，特别是调节甲状腺激素诱导的基因表达，将变得清晰。

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.