Expression and structure of senescence marker protein-30 (SMP30) and its biological significance.

We previously identified a novel protein, the amounts of which are down-regulated in an androgen-independent manner with aging in the rat liver. We designated this protein as senescence marker protein-30 (SMP30). SMP30 is preferentially expressed in cytosol of hepatocytes and renal tubular epithelia, and its expression is maintained at high level throughout the tissue maturing stage as well as young and adult stages, but decreases during senescent stages in both sexes. Subsequently, we cloned cDNAs encoding SMP30 from rat, human and mouse and found that the amino acid sequence of SMP30 is well conserved with remarkable homology among these species. We also determined the genome organization and 5' flanking region of SMP30 in mouse genome. In the meantime, SMP30 turned out to be identical to a Ca2+-binding protein called regucaltin. In order to elucidate the functional significance of SMP30, we have generated Hep G2 cells that stably express large amounts of SMP30 by transfecting human SMP30 cDNA. Cell biological analyses on these SMP30 transfectants suggest that SMP30 regulates Ca2+ homeostasis by enhancing plasma membrane Ca2+-pumping activity in Hep G2 cells. This result implies that the down-regulation of SMP30 may contribute to hepatic deterioration of cellular functions during aging. In this review, we present a overview of SMP30 in its structure, expression and possible physiological roles. We also discuss hypothetical role(s) of SMP30 in aging and Ca2+ homeostasis.