Role of calcium-binding protein regucalcin in regenerating rat liver.

Regucalcin is a novel calcium-binding protein which does not contain EF-hand motif as a Ca2+-binding domain. The organization of the rat regucalcin gene consists of seven exons and six introns. Its mRNA is mainly present in liver but slightly in kidney with a size of 1.8 kb. Hepatic regucalcin mRNA expression is stimulated by various factors including calcium, calcitonin, insulin, and oestrogen in rats. The mRNA is also expressed in hepatoma cells (Morris hepatoma and HepG2). Regucalcin plays a role in the maintenance of cytosolic Ca2+ homeostasis in liver cells. Moreover, regucalcin has an inhibitory effect on Ca2+/calmodulin-dependent enzyme activation, protein kinase C activation, and many Ca2+-activated enzymes, indicating a role in the regulation of the Ca2+-signalling system. Recently, regucalcin has been demonstrated to regulate nuclear function in liver cells. Regucalcin can inhibit Ca2+-activated nuclear DNA fragmentation in rat isolated liver nuclei. Furthermore, the liver nuclear DNA and RNA syntheses are inhibited by regucalcin. Such an effect of regucalcin is also seen in the nuclei of regenerating rat liver. The regucalcin mRNA level is increased in regenerating liver. These findings suggest that regucalcin plays a regulatory role in the suppression for overexpression of proliferative cells.