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Review
. 2014 Sep 5;19(9):13976-89.
doi: 10.3390/molecules190913976.

Sorcin, a calcium binding protein involved in the multidrug resistance mechanisms in cancer cells

Gianni Colotti  1 , Elena Poser  2 , Annarita Fiorillo  3 , Ilaria Genovese  4 , Valerio Chiarini  5 , Andrea Ilari  6
Affiliations
Review

Sorcin, a calcium binding protein involved in the multidrug resistance mechanisms in cancer cells

Gianni Colotti et al. Molecules. .

Abstract

Sorcin is a penta-EF hand calcium binding protein, which participates in the regulation of calcium homeostasis in cells. Sorcin regulates calcium channels and exchangers located at the plasma membrane and at the endo/sarcoplasmic reticulum (ER/SR), and allows high levels of calcium in the ER to be maintained, preventing ER stress and possibly, the unfolded protein response. Sorcin is highly expressed in the heart and in the brain, and overexpressed in many cancer cells. Sorcin gene is in the same amplicon as other genes involved in the resistance to chemotherapeutics in cancer cells (multi-drug resistance, MDR) such as ABCB4 and ABCB1; its overexpression results in increased drug resistance to a number of chemotherapeutic agents, and inhibition of sorcin expression by sorcin-targeting RNA interference leads to reversal of drug resistance. Sorcin is increasingly considered a useful marker of MDR and may represent a therapeutic target for reversing tumor multidrug resistance.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Sequence alignment of human PEF proteins of known crystal structures. Sorcin (NP_003121), grancalcin (NP_036330), PDCD6 (NP_037364), and small and large M-calpain chains are shown. The residues in the N-terminal domain are indicated as lowercase; the residues of the C-terminal calcium binding domain are indicated as uppercase. Structural alignment of EF-hands and of alpha-helices is reported. Glu53, Glu94, Trp99, Trp105, Phe112 and Glu124 are indicated in bold and blue.
Figure 2
Figure 2
Primary and secondary structure (A) and crystallographic X-ray structure of the human sorcin calcium binding C-terminal domain (B) (PDB: 1JUO). The residues involved in the contact with targets, according to Ilari et al., 2002, are in bold, colored blue. The residues mutated to analyze the mechanism of activation of sorcin (W99, W105, E53, E94, E124, F112) are underlined. The two monomers in the SCBD dimer are depicted in different shades of gray; the D-helix is indicated in blue; W99 and W105 are blue, F112 is green, E124 is red. Right: Only one SCBD monomer is shown, rotated 90° with respect to the dimer shown on the left.
Figure 3
Figure 3
Sorcin inhibits the ryanodine receptor and up-regulates SERCA, increasing calcium load of the endoplasmic reticulum.
See this image and copyright information in PMC

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