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

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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.