Nicotinamide Adenine Dinucleotide Phosphate-Dependent Cytosolic T3 Binding Protein as a Regulator for T3-Mediated Transactivation

Nicotinamide adenine dinucleotide phosphate (NADPH)- dependent cytosolic T3 binding protein (CTBP) plays a role in the regulation of nuclear transport of T3 in vitro. However, it is not known whether CTBP regulates the T3 action. In this study, we examined the effects of CTBP on cellular translocation of T3 and on transcriptional activation using established CTBP-expressing CHO or GH3 cells. The expression of CTBP increased cellular and nuclear uptake of T3 in the CTBP-expressing cells. The efflux rate was decreased by induction of CTBP. Efflux from nuclei also inhibited by induction of CTBP. Expression of CTBP suppressed the T3-regulated luciferase activity in GH3 cells. Suppression was observed to be related to the expression level of CTBP. T3 induction of rat GH mRNA was lower in the cells expressing CTBP than that in CTBP-null cells. These results suggest that CTBP regulates the T3-induced gene expression, with which an increase in the nuclear content of the T3 is associated. Because we observed that a part of CTBP could be transported into nuclei and that acceptor protein for CTBP is present in nuclei as previously reported, interaction of CTBP with certain proteins, including transcription factors or nuclear T3 receptor, may contribute to the regulation.