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. 2013 Oct;18(10):1145-53.
doi: 10.1007/s10495-013-0859-x.

The Anti-Apoptotic Effect of Regucalcin Is Mediated Through Multisignaling Pathways

Free PMC article

The Anti-Apoptotic Effect of Regucalcin Is Mediated Through Multisignaling Pathways

Masayoshi Yamaguchi. Apoptosis. .
Free PMC article


Regucalcin (RGN/SMP30) was originally discovered in 1978 as a calcium-binding protein that does not contain the EF-hand motif of as a calcium-binding domain. The name, regucalcin, was proposed for this calcium-binding protein, which can regulate various Ca(2+)-dependent enzymes activation in liver cells. The regucalcin gene is localized on the X chromosome, and its expression is mediated through many signaling factors. Regucalcin plays a pivotal role in regulation of intracellular calcium homeostasis in various cell types. Regucalcin also has a suppressive effect on various signaling pathways from the cytoplasm to nucleus in proliferating cells and regulates nuclear function in including deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) synthesis. Overexpression of endogenous regucalcin was found to suppress apoptosis in modeled rat hepatoma cells and normal rat kidney proximal epithelial NRK52 cells induced by various signaling factors. Suppressive effect of regucalcin on apoptosis is related to inhibition of nuclear Ca(2+)-activated DNA fragmentation, Ca(2+)/calmodulin-dependent nitric oxide synthase, caspase-3, Bax, cytochrome C, protein tyrosine kinase, protein tyrosine phosphatase in the cytoplasm and nucleus. Moreover, regucalcin stimulates Bcl-2 mRNA expression and depresses enhancement of caspase-3, Apaf-1 and Akt-1 mRNAs expression. This review discusses that regucalcin plays a pivotal role in rescue of apoptotic cell death, which is mediated through various signaling factors.


Fig. 1
Fig. 1
Regucalcin plays a role as suppressor in cell death and apoptosis induced through various signaling factors (including TNF-α, TGF-β, insulin, IGF-I, LPS, PD98059, dibucaine, thapsigargin, Bay K 8644, or sulforaphane). Protective effect of regucalcin on cell death and apoptosis is mediated through suppressive effects on the activities of NO synthase, protein kinase, protein phosphatase, caspase-3, or Ca2+-dependent and independent endonuclease and stimulatory effects on the expressions of Bcl-2 and Akt-1 mRNAs in normal cells and cancer cells

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