The role of endogenous regucalcin, a regulatory protein of Ca2+ signaling, in the regulation of liver nuclear function was investigated by using regucalcin transgenic (TG) rats. Regucalcin levels were significantly increased in the liver nuclei of regucalcin TG male and female rats. Nuclear protein tyrosine phosphatase activity was significantly elevated in the presence of anti-regucalcin monoclonal antibody (50 ng/ml) in the reaction mixture containing liver nuclear protein obtained from normal (wt) rats. This increase was significantly prevented in the liver nuclei of regucalcin TG rats. Moreover, nuclear ribonucleic acid (RNA) synthesis was significantly suppressed in the liver nuclei of regucalcin TG rats as compared with that of normal rats. The effect of calcium chloride (10 micro M) or anti-regucalcin monoclonal antibody (50 ng/ml) in increasing RNA synthesis was completely blocked in the liver nuclei of the TG rats. These results suggest that endogenous regucalcin plays a suppressive role in the regulation of liver nuclear function in rats.