The role of regucalcin in nuclear regulation of regenerating liver

Regucalcin was discovered in 1978 as a Ca(2+)-binding protein that does not contain EF-hand motif of Ca(2+)- binding domain [Yamaguchi, M., and Yamamoto T., Chem. Pharm. Bull. 26, 1915-1918, 1978]. The name regucalcin was proposed for this Ca(2+)-binding protein, which can regulate liver cell functions related to Ca(2+). Regucalcin has been demonstrated to play a multifunctional role in liver and kidney cells, for which regucalcin mRNA expression and its protein content are pronounced. Hepatic regucalcin mRNA expression has been shown to be mediated through signaling pathway of Ca(2+)/calmodulin-dependent protein kinase, protein kinase C, and tyrosine kinase. AP-1- and NF-1-like factors can bind to the promotor region of the rat regucalcin gene to mediate the Ca(2+) response for transcriptional activation. Growing evidence supports the view, moreover, that regucalcin plays an important role in the regulation of Ca(2+) signaling from the cytoplasm to nuclei in the proliferative cells of regenerating rat liver. Also, regucalcin has been demonstrated to be transported to liver nucleus, and it can inhibit nuclear protein kinase, protein phosphatase, and DNA and RNA synthesis in regenerating liver. Regucalcin plays a physiologic role in the control for overexpression of proliferative cells. Regucalcin has been proposed to be an important regulatory protein in nuclear signaling system. (C) 2000 Academic Press.