The calpain system and cancer (original) (raw)

• Guroff, G. A neutral, calcium-activated proteinase from the soluble fraction of rat brain. J. Biol. Chem. 239, 149–155 (1964).
  CAS PubMed Google Scholar
• Croall, D. E. & DeMartino, G. N. Calcium-activated neutral protease (calpain) system: structure, function, and regulation. Physiol. Rev. 71, 813–847 (1991).
  CAS PubMed Google Scholar
• Sorimachi, H., Hata, S. & Ono, Y. Expanding members and roles of the calpain superfamily and their genetically modified animals. Exp. Anim. 59, 549–566 (2010).
  CAS PubMed Google Scholar
• Goll, D. E., Thompson, V. F., Li, H., Wei, W. & Cong, J. The calpain system. Physiol. Rev. 83, 731–801 (2003).
  CAS PubMed Google Scholar
• Dayton, W. R., Schollmeyer, J. V., Lepley, R. A. & Cortes, L. R. A calcium-activated protease possibly involved in myofibrillar protein turnover. Isolation of a low-calcium-requiring form of the protease. Biochim. Biophys. Acta 659, 48–61 (1981).
  CAS PubMed Google Scholar
• Mellgren, R. L. Canine cardiac calcium-dependent proteases: resolution of two forms with different requirements for calcium. FEBS Lett. 109, 129–133 (1980).
  CAS PubMed Google Scholar
• Inomata, M., Hayashi, M., Nakamura, M., Imahori, K. & Kawashima, S. Purification and characterization of a calcium-activated neutral protease from rabbit skeletal muscle which requires calcium ions of microM order concentration. J. Biochem. 93, 291–294 (1983).
  CAS PubMed Google Scholar
• Cong, J., Goll, D. E., Peterson, A. M. & Kapprell, H. P. The role of autolysis in activity of the Ca2+-dependent proteinases (mu-calpain and m-calpain). J. Biol. Chem. 264, 10096–10103 (1989).
  CAS PubMed Google Scholar
• Edmunds, T., Nagainis, P. A., Sathe, S. K., Thompson, V. F. & Goll, D. E. Comparison of the autolyzed and unautolyzed forms of mu- and m-calpain from bovine skeletal muscle. Biochim. Biophys. Acta 1077, 197–208 (1991).
  CAS PubMed Google Scholar
• Coolican, S. A. & Hathaway, D. R. Effect of L-α-phosphatidylinositol on a vascular smooth muscle Ca2+-dependent protease. Reduction of the Ca2+ requirement for autolysis. J. Biol. Chem. 259, 11627–11630 (1984).
  CAS PubMed Google Scholar
• Imajoh, S., Kawasaki, H. & Suzuki, K. The amino-terminal hydrophobic region of the small subunit of calcium-activated neutral protease (CANP) is essential for its activation by phosphatidylinositol. J. Biochem. 99, 1281–1284 (1986).
  CAS PubMed Google Scholar
• Saido, T. C., Mizuno, K. & Suzuki, K. Proteolysis of protein kinase C by calpain: effect of acidic phospholipids. Biomed. Biochim. Acta 50, 485–489 (1991).
  CAS PubMed Google Scholar
• Saido, T. C., Shibata, M., Takenawa, T., Murofushi, H. & Suzuki, K. Positive regulation of mu-calpain action by polyphosphoinositides. J. Biol. Chem. 267, 24585–24590 (1992).
  CAS PubMed Google Scholar
• Aoki, K. et al. Complete amino acid sequence of the large subunit of the low-Ca2+-requiring form of human Ca2+-activated neutral protease (muCANP) deduced from its cDNA sequence. FEBS Lett. 205, 313–317 (1986).
  CAS PubMed Google Scholar
• Imajoh, S. et al. Molecular cloning of the cDNA for the large subunit of the high-Ca2+-requiring form of human Ca2+-activated neutral protease. Biochemistry 27, 8122–8128 (1988).
  CAS PubMed Google Scholar
• Ohno, S. et al. Evolutionary origin of a calcium-dependent protease by fusion of genes for a thiol protease and a calcium-binding protein? Nature 312, 566–570 (1984).
  CAS PubMed Google Scholar
• Kawasaki, H., Imajoh, S., Kawashima, S., Hayashi, H. & Suzuki, K. The small subunits of calcium dependent proteases with different calcium sensitivities are identical. J. Biochem. 99, 1525–1532 (1986).
  CAS PubMed Google Scholar
• Ohno, S., Emori, Y. & Suzuki, K. Nucleotide sequence of a cDNA coding for the small subunit of human calcium-dependent protease. Nucleic Acids Res. 14, 5559 (1986).
  CAS PubMed PubMed Central Google Scholar
• Hosfield, C. M., Elce, J. S., Davies, P. L. & Jia, Z. Crystal structure of calpain reveals the structural basis for Ca2+-dependent protease activity and a novel mode of enzyme activation. EMBO J. 18, 6880–6889 (1999). This work showed the calcium-free structure of calpain, which can be used to explain enzymatic inactivity in the absence of calcium.
  CAS PubMed PubMed Central Google Scholar
• Strobl, S. et al. The crystal structure of calcium-free human m-calpain suggests an electrostatic switch mechanism for activation by calcium. Proc. Natl Acad. Sci. USA 97, 588–592 (2000). This study investigated the structure of calpain without calcium, and describes the formation of a catalytic centre.
  CAS PubMed PubMed Central Google Scholar
• Hanna, R. A., Campbell, R. L. & Davies, P. L. Calcium-bound structure of calpain and its mechanism of inhibition by calpastatin. Nature 456, 409–412 (2008). This structural study shows the potent nature of specific calpastatin inhibition of up to four calpain molecules and the calcium-mediated conformational change.
  CAS PubMed Google Scholar
• Moldoveanu, T., Gehring, K. & Green, D. R. Concerted multi-pronged attack by calpastatin to occlude the catalytic cleft of heterodimeric calpains. Nature 456, 404–408 (2008). This structural study shows the calcium-mediated conformational changes that are required for calpastatin inhibition of calpain.
  CAS PubMed PubMed Central Google Scholar
• Minami, Y., Emori, Y., Kawasaki, H. & Suzuki, K. E-F hand structure-domain of calcium-activated neutral protease (CANP) can bind Ca2+ ions. J. Biochem. 101, 889–895 (1987).
  CAS PubMed Google Scholar
• Imajoh, S., Kawasaki, H. & Suzuki, K. The COOH-terminal E-F hand structure of calcium-activated neutral protease (CANP) is important for the association of subunits and resulting proteolytic activity. J. Biochem. 101, 447–452 (1987).
  CAS PubMed Google Scholar
• Blanchard, H. et al. Structure of a calpain Ca2+-binding domain reveals a novel EF-hand and Ca2+-induced conformational changes. Nature Struct. Biol. 4, 532–538 (1997).
  CAS PubMed Google Scholar
• Azam, M. et al. Disruption of the mouse mu-calpain gene reveals an essential role in platelet function. Mol. Cell. Biol. 21, 2213–2220 (2001).
  CAS PubMed PubMed Central Google Scholar
• Dutt, P. et al. m-Calpain is required for preimplantation embryonic development in mice. BMC Dev. Biol. 6, 3 (2006).
  PubMed PubMed Central Google Scholar
• Arthur, J. S., Elce, J. S., Hegadorn, C., Williams, K. & Greer, P. A. Disruption of the murine calpain small subunit gene, Capn4: calpain is essential for embryonic development but not for cell growth and division. Mol. Cell. Biol. 20, 4474–4481 (2000).
  CAS PubMed PubMed Central Google Scholar
• Imajoh, S., Kawasaki, H. & Suzuki, K. Limited autolysis of calcium-activated neutral protease (CANP): reduction of the Ca2+-requirement is due to the NH2-terminal processing of the large subunit. J. Biochem. 100, 633–642 (1986).
  CAS PubMed Google Scholar
• Suzuki, K., Tsuji, S., Kubota, S., Kimura, Y. & Imahori, K. Limited autolysis of Ca2+-activated neutral protease (CANP) changes its sensitivity to Ca2+ ions. J. Biochem. 90, 275–278 (1981).
  CAS PubMed Google Scholar
• Pontremoli, S. et al. An endogenous activator of the Ca2+-dependent proteinase of human neutrophils that increases its affinity for Ca2+. Proc. Natl Acad. Sci. USA 85, 1740–1743 (1988).
  CAS PubMed PubMed Central Google Scholar
• Pontremoli, S. et al. Identification of an endogenous activator of calpain in rat skeletal muscle. Biochem. Biophys. Res. Commun. 171, 569–574 (1990).
  CAS PubMed Google Scholar
• Salamino, F. et al. Site-directed activation of calpain is promoted by a membrane-associated natural activator protein. Biochem. J. 290, 191–197 (1993).
  CAS PubMed PubMed Central Google Scholar
• Melloni, E., Michetti, M., Salamino, F. & Pontremoli, S. Molecular and functional properties of a calpain activator protein specific for mu-isoforms. J. Biol. Chem. 273, 12827–12831 (1998).
  CAS PubMed Google Scholar
• Xu, L. & Deng, X. Protein kinase Ciota promotes nicotine-induced migration and invasion of cancer cells via phosphorylation of micro- and m-calpains. J. Biol. Chem. 281, 4457–4466 (2006).
  CAS PubMed Google Scholar
• Glading, A., Uberall, F., Keyse, S. M., Lauffenburger, D. A. & Wells, A. Membrane proximal ERK signaling is required for M-calpain activation downstream of epidermal growth factor receptor signaling. J. Biol. Chem. 276, 23341–23348 (2001). This study demonstrated that m-calpain can be activated by ERK during EGFR signalling.
  CAS PubMed Google Scholar
• Smith, S. D., Jia, Z., Huynh, K. K., Wells, A. & Elce, J. S. Glutamate substitutions at a PKA consensus site are consistent with inactivation of calpain by phosphorylation. FEBS Lett. 542, 115–118 (2003).
  CAS PubMed Google Scholar
• Shiraha, H., Glading, A., Chou, J., Jia, Z. & Wells, A. Activation of m-calpain (calpain II) by epidermal growth factor is limited by protein kinase A phosphorylation of m-calpain. Mol. Cell. Biol. 22, 2716–2727 (2002).
  CAS PubMed PubMed Central Google Scholar
• Leloup, L. et al. m-Calpain activation is regulated by its membrane localization and by its binding to phosphatidylinositol 4, 5-bisphosphate. J. Biol. Chem. 285, 33549–33566 (2010).
  CAS PubMed PubMed Central Google Scholar
• Shao, H. et al. Spatial localization of m-calpain to the plasma membrane by phosphoinositide biphosphate binding during epidermal growth factor receptor-mediated activation. Mol. Cell. Biol. 26, 5481–5496 (2006).
  CAS PubMed PubMed Central Google Scholar
• Goudenege, S., Poussard, S., Dulong, S. & Cottin, P. Biologically active milli-calpain associated with caveolae is involved in a spatially compartmentalised signalling involving protein kinase C α and myristoylated alanine-rich C-kinase substrate (MARCKS). Int. J. Biochem. Cell Biol. 37, 1900–1910 (2005).
  CAS PubMed Google Scholar
• Kifor, O., Kifor, I., Moore, F. D. Jr, Butters, R. R. Jr & Brown, E. M. m-Calpain colocalizes with the calcium-sensing receptor (CaR) in caveolae in parathyroid cells and participates in degradation of the CaR. J. Biol. Chem. 278, 31167–31176 (2003).
  CAS PubMed Google Scholar
• Garcia, M., Bondada, V. & Geddes, J. W. Mitochondrial localization of mu-calpain. Biochem. Biophys. Res. Commun. 338, 1241–1247 (2005).
  CAS PubMed Google Scholar
• Badugu, R., Garcia, M., Bondada, V., Joshi, A. & Geddes, J. W. N. terminus of calpain 1 is a mitochondrial targeting sequence. J. Biol. Chem. 283, 3409–3417 (2008).
  CAS PubMed Google Scholar
• Kar, P., Chakraborti, T., Samanta, K. & Chakraborti, S. Submitochondrial localization of associated mu-calpain and calpastatin. Arch. Biochem. Biophys. 470, 176–186 (2008).
  CAS PubMed Google Scholar
• Wendt, A., Thompson, V. F. & Goll, D. E. Interaction of calpastatin with calpain: a review. Biol. Chem. 385, 465–472 (2004).
  CAS PubMed Google Scholar
• Hanna, R. A., Garcia-Diaz, B. E. & Davies, P. L. Calpastatin simultaneously binds four calpains with different kinetic constants. FEBS Lett. 581, 2894–2898 (2007).
  CAS PubMed Google Scholar
• Kapprell, H. P. & Goll, D. E. Effect of Ca2+ on binding of the calpains to calpastatin. J. Biol. Chem. 264, 17888–17896 (1989).
  CAS PubMed Google Scholar
• Averna, M. et al. Changes in calpastatin localization and expression during calpain activation: a new mechanism for the regulation of intracellular Ca2+-dependent proteolysis. Cell. Mol. Life Sci. 60, 2669–2678 (2003).
  CAS PubMed Google Scholar
• De Tullio, R., Sparatore, B., Salamino, F., Melloni, E. & Pontremoli, S. Rat brain contains multiple mRNAs for calpastatin. FEBS Lett. 422, 113–117 (1998).
  CAS PubMed Google Scholar
• Parr, T. et al. Expression of calpastatin isoforms in muscle and functionality of multiple calpastatin promoters. Arch. Biochem. Biophys. 427, 8–15 (2004).
  CAS PubMed Google Scholar
• Parr, T., Sensky, P. L., Bardsley, R. G. & Buttery, P. J. Calpastatin expression in porcine cardiac and skeletal muscle and partial gene structure. Arch. Biochem. Biophys. 395, 1–13 (2001).
  CAS PubMed Google Scholar
• Raynaud, P., Jayat-Vignoles, C., Laforet, M. P., Leveziel, H. & Amarger, V. Four promoters direct expression of the calpastatin gene. Arch. Biochem. Biophys. 437, 69–77 (2005).
  CAS PubMed Google Scholar
• Takano, J., Kawamura, T., Murase, M., Hitomi, K. & Maki, M. Structure of mouse calpastatin isoforms: implications of species-common and species-specific alternative splicing. Biochem. Biophys. Res. Commun. 260, 339–345 (1999).
  CAS PubMed Google Scholar
• Takano, J., Watanabe, M., Hitomi, K. & Maki, M. Four types of calpastatin isoforms with distinct amino-terminal sequences are specified by alternative first exons and differentially expressed in mouse tissues. J. Biochem. 128, 83–92 (2000).
  CAS PubMed Google Scholar
• Cong, M., Thompson, V. F., Goll, D. E. & Antin, P. B. The bovine calpastatin gene promoter and a new N-terminal region of the protein are targets for cAMP-dependent protein kinase activity. J. Biol. Chem. 273, 660–666 (1998).
  CAS PubMed Google Scholar
• Sensky, P. L. et al. Effect of anabolic agents on calpastatin promoters in porcine skeletal muscle and their responsiveness to cyclic adenosine monophosphate- and calcium-related stimuli. J. Anim. Sci. 84, 2973–2982 (2006).
  CAS PubMed Google Scholar
• Geesink, G. H., Nonneman, D. & Koohmaraie, M. An improved purification protocol for heart and skeletal muscle calpastatin reveals two isoforms resulting from alternative splicing. Arch. Biochem. Biophys. 356, 19–24 (1998).
  CAS PubMed Google Scholar
• Raynaud, P. et al. Correlation between bovine calpastatin mRNA transcripts and protein isoforms. Arch. Biochem. Biophys. 440, 46–53 (2005).
  CAS PubMed Google Scholar
• De Tullio, R. et al. Multiple rat brain calpastatin forms are produced by distinct starting points and alternative splicing of the N-terminal exons. Arch. Biochem. Biophys. 465, 148–156 (2007).
  CAS PubMed Google Scholar
• De Tullio, R. et al. Involvement of exon 6-mediated calpastatin intracellular movements in the modulation of calpain activation. Biochim. Biophys. Acta 1790, 182–187 (2009).
  CAS PubMed Google Scholar
• Lee, W. J. et al. Molecular diversity in amino-terminal domains of human calpastatin by exon skipping. J. Biol. Chem. 267, 8437–8442 (1992). This work described the exon skipping that occurs in calpastatin resulting in a large number of variants.
  CAS PubMed Google Scholar
• Minobe, E. et al. A region of calpastatin domain L that reprimes cardiac L-type Ca2+ channels. Biochem. Biophys. Res. Commun. 348, 288–294 (2006).
  CAS PubMed Google Scholar
• Averna, M. et al. Changes in intracellular calpastatin localization are mediated by reversible phosphorylation. Biochem. J. 354, 25–30 (2001).
  CAS PubMed PubMed Central Google Scholar
• Averna, M. et al. Age-dependent degradation of calpastatin in kidney of hypertensive rats. J. Biol. Chem. 276, 38426–38432 (2001).
  CAS PubMed Google Scholar
• Parr, T., Sensky, P. L., Arnold, M. K., Bardsley, R. G. & Buttery, P. J. Effects of epinephrine infusion on expression of calpastatin in porcine cardiac and skeletal muscle. Arch. Biochem. Biophys. 374, 299–305 (2000).
  CAS PubMed Google Scholar
• Salamino, F. et al. Modulation of rat brain calpastatin efficiency by post-translational modifications. FEBS Lett. 412, 433–438 (1997).
  CAS PubMed Google Scholar
• Tullio, R. D. et al. Changes in intracellular localization of calpastatin during calpain activation. Biochem. J. 343, 467–472 (1999).
  PubMed PubMed Central Google Scholar
• Kimura, Y. et al. The involvement of calpain-dependent proteolysis of the tumor suppressor NF2 (merlin) in schwannomas and meningiomas. Nature Med. 4, 915–922 (1998).
  CAS PubMed Google Scholar
• Braun, C. et al. Expression of calpain I messenger RNA in human renal cell carcinoma: correlation with lymph node metastasis and histological type. Int. J. Cancer 84, 6–9 (1999).
  CAS PubMed Google Scholar
• Lakshmikuttyamma, A., Selvakumar, P., Kanthan, R., Kanthan, S. C. & Sharma, R. K. Overexpression of m-calpain in human colorectal adenocarcinomas. Cancer Epidemiol. Biomarkers Prev. 13, 1604–1609 (2004).
  CAS PubMed Google Scholar
• Reichrath, J. et al. Different expression patterns of calpain isozymes 1 and 2 (CAPN1 and 2) in squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) of human skin. J. Pathol. 199, 509–516 (2003).
  CAS PubMed Google Scholar
• Mamoune, A., Luo, J. H., Lauffenburger, D. A. & Wells, A. Calpain-2 as a target for limiting prostate cancer invasion. Cancer Res. 63, 4632–4640 (2003).
  CAS PubMed Google Scholar
• Rios-Doria, J. et al. The role of calpain in the proteolytic cleavage of E-cadherin in prostate and mammary epithelial cells. J. Biol. Chem. 278, 1372–1379 (2003).
  CAS PubMed Google Scholar
• Salehin, D. et al. Immunhistochemical analysis for expression of calpain 1, calpain 2 and calpastatin in endometrial cancer. Anticancer Res. 30, 2837–2843 (2010).
  CAS PubMed Google Scholar
• Lee, S. J. et al. Increased expression of calpain 6 in uterine sarcomas and carcinosarcomas: an immunohistochemical analysis. Int. J. Gynecol. Cancer 17, 248–253 (2007).
  PubMed Google Scholar
• Lee, S. J., Kim, B. G., Choi, Y. L. & Lee, J. W. Increased expression of calpain 6 during the progression of uterine cervical neoplasia: immunohistochemical analysis. Oncol. Rep. 19, 859–863 (2008).
  PubMed Google Scholar
• Moretti, D. et al. Novel variants of muscle calpain 3 identified in human melanoma cells: cisplatin-induced changes in vitro and differential expression in melanocytic lesions. Carcinogenesis 30, 960–967 (2009).
  CAS PubMed Google Scholar
• Yoshikawa, Y., Mukai, H., Hino, F., Asada, K. & Kato, I. Isolation of two novel genes, down-regulated in gastric cancer. Jpn J. Cancer Res. 91, 459–463 (2000).
  CAS PubMed PubMed Central Google Scholar
• Moreno-Luna, R. et al. Calpain 10 gene and laryngeal cancer: a survival analysis. Head Neck 33, 72–76 (2011).
  PubMed Google Scholar
• Frances, C. P. et al. Identification of a protective haplogenotype within CAPN10 gene influencing colorectal cancer susceptibility. J. Gastroenterol. Hepatol. 22, 2298–2302 (2007).
  CAS PubMed Google Scholar
• Fong, P. Y. et al. Association of diabetes susceptibility gene calpain-10 with pancreatic cancer among smokers. J. Gastrointest. Cancer 41, 203–208 (2010).
  CAS PubMed PubMed Central Google Scholar
• Hill, J. W., Hu, J. J. & Evans, M. K. OGG1 is degraded by calpain following oxidative stress and cisplatin exposure. DNA Repair 7, 648–654 (2008).
  CAS PubMed PubMed Central Google Scholar
• Zhou, J., Kohl, R., Herr, B., Frank, R. & Brune, B. Calpain mediates a von Hippel-Lindau protein-independent destruction of hypoxia-inducible factor-1α. Mol. Biol. Cell 17, 1549–1558 (2006).
  CAS PubMed PubMed Central Google Scholar
• Huttenlocher, A., Sandborg, R. R. & Horwitz, A. F. Adhesion in cell migration. Curr. Opin. Cell Biol. 7, 697–706 (1995).
  CAS PubMed Google Scholar
• Beckerle, M. C., Burridge, K., DeMartino, G. N. & Croall, D. E. Colocalization of calcium-dependent protease II and one of its substrates at sites of cell adhesion. Cell 51, 569–577 (1987). Interesting study that identified m-calpain localized to integrin-associated focal adhesion structures and directly cleaved the focal adhesion protein talin.
  CAS PubMed Google Scholar
• Cuevas, B. D. et al. MEKK1 regulates calpain-dependent proteolysis of focal adhesion proteins for rear-end detachment of migrating fibroblasts. EMBO J. 22, 3346–3355 (2003).
  CAS PubMed PubMed Central Google Scholar
• Huttenlocher, A. et al. Regulation of cell migration by the calcium-dependent protease calpain. J. Biol. Chem. 272, 32719–32722 (1997).
  CAS PubMed Google Scholar
• Xu, L. & Deng, X. Suppression of cancer cell migration and invasion by protein phosphatase 2A through dephosphorylation of mu- and m-calpains. J. Biol. Chem. 281, 35567–35575 (2006).
  CAS PubMed Google Scholar
• Postovit, L. M. et al. Calpain is required for MMP-2 and u-PA expression in SV40 large T-antigen-immortalized cells. Biochem. Biophys. Res. Commun. 297, 294–301 (2002).
  CAS PubMed Google Scholar
• Carragher, N. O. et al. v-Src-induced modulation of the calpain-calpastatin proteolytic system regulates transformation. Mol. Cell. Biol. 22, 257–269 (2002).
  CAS PubMed PubMed Central Google Scholar
• Carragher, N. O., Fonseca, B. D. & Frame, M. C. Calpain activity is generally elevated during transformation but has oncogene-specific biological functions. Neoplasia 6, 53–73 (2004).
  CAS PubMed PubMed Central Google Scholar
• Chan, K. T., Bennin, D. A. & Huttenlocher, A. Regulation of adhesion dynamics by calpain-mediated proteolysis of focal adhesion kinase (FAK). J. Biol. Chem. 285, 11418–11426 (2010).
  CAS PubMed PubMed Central Google Scholar
• Franco, S. J. et al. Calpain-mediated proteolysis of talin regulates adhesion dynamics. Nature Cell Biol. 6, 977–983 (2004).
  CAS PubMed Google Scholar
• Yamaguchi, R., Maki, M., Hatanaka, M. & Sabe, H. Unphosphorylated and tyrosine-phosphorylated forms of a focal adhesion protein, paxillin, are substrates for calpain II in vitro: implications for the possible involvement of calpain II in mitosis-specific degradation of paxillin. FEBS Lett. 356, 114–116 (1994).
  CAS PubMed Google Scholar
• Carragher, N. O., Levkau, B., Ross, R. & Raines, E. W. Degraded collagen fragments promote rapid disassembly of smooth muscle focal adhesions that correlates with cleavage of pp125(FAK), paxillin, and talin. J. Cell Biol. 147, 619–630 (1999).
  CAS PubMed PubMed Central Google Scholar
• Franco, S., Perrin, B. & Huttenlocher, A. Isoform specific function of calpain 2 in regulating membrane protrusion. Exp. Cell Res. 299, 179–187 (2004).
  CAS PubMed Google Scholar
• Liu, X. & Schnellmann, R. G. Calpain mediates progressive plasma membrane permeability and proteolysis of cytoskeleton-associated paxillin, talin, and vinculin during renal cell death. J. Pharmacol. Exp. Ther. 304, 63–70 (2003).
  CAS PubMed Google Scholar
• Saido, T. C. et al. Spatial resolution of fodrin proteolysis in postischemic brain. J. Biol. Chem. 268, 25239–25243 (1993).
  CAS PubMed Google Scholar
• Sato, K. et al. Degradation of fodrin by m-calpain in fibroblasts adhering to fibrillar collagen I gel. J. Biochem. 136, 777–785 (2004).
  CAS PubMed Google Scholar
• Wang, H. et al. PKA-mediated protein phosphorylation protects ezrin from calpain I cleavage. Biochem. Biophys. Res. Commun. 333, 496–501 (2005).
  CAS PubMed Google Scholar
• Shuster, C. B. & Herman, I. M. Indirect association of ezrin with F-actin: isoform specificity and calcium sensitivity. J. Cell Biol. 128, 837–848 (1995).
  CAS PubMed Google Scholar
• Yao, X., Thibodeau, A. & Forte, J. G. Ezrin-calpain I interactions in gastric parietal cells. Am. J. Physiol. 265, C36–C46 (1993).
  CAS PubMed Google Scholar
• Serrano, K. & Devine, D. V. Vinculin is proteolyzed by calpain during platelet aggregation: 95 kDa cleavage fragment associates with the platelet cytoskeleton. Cell Motil. Cytoskeleton 58, 242–252 (2004).
  CAS PubMed Google Scholar
• Selliah, N., Brooks, W. H. & Roszman, T. L. Proteolytic cleavage of α-actinin by calpain in T cells stimulated with anti-CD3 monoclonal antibody. J. Immunol. 156, 3215–3221 (1996).
  CAS PubMed Google Scholar
• Raynaud, F. et al. The calpain 1-α-actinin interaction. Resting complex between the calcium-dependent protease and its target in cytoskeleton. Eur. J. Biochem. 270, 4662–4670 (2003).
  CAS PubMed Google Scholar
• Cortesio, C. L., Boateng, L. R., Piazza, T. M., Bennin, D. A. & Huttenlocher, A. Calpain-mediated proteolysis of paxillin negatively regulates focal adhesion dynamics and cell migration. J. Biol. Chem. 286, 9998–10006 (2011).
  CAS PubMed PubMed Central Google Scholar
• Lebart, M. C. & Benyamin, Y. Calpain involvement in the remodeling of cytoskeletal anchorage complexes. FEBS J. 273, 3415–3426 (2006).
  CAS PubMed Google Scholar
• Glading, A., Lauffenburger, D. A. & Wells, A. Cutting to the chase: calpain proteases in cell motility. Trends Cell Biol. 12, 46–54 (2002).
  CAS PubMed Google Scholar
• Robles, E., Huttenlocher, A. & Gomez, T. M. Filopodial calcium transients regulate growth cone motility and guidance through local activation of calpain. Neuron 38, 597–609 (2003).
  CAS PubMed Google Scholar
• Roumes, H. et al. Calpains: markers of tumor aggressiveness? Exp. Cell Res. 316, 1587–1599 (2010).
  CAS PubMed Google Scholar
• Perrin, B. J., Amann, K. J. & Huttenlocher, A. Proteolysis of cortactin by calpain regulates membrane protrusion during cell migration. Mol. Biol. Cell 17, 239–250 (2006).
  CAS PubMed PubMed Central Google Scholar
• Wolf, K. et al. Compensation mechanism in tumor cell migration: mesenchymal-amoeboid transition after blocking of pericellular proteolysis. J. Cell Biol. 160, 267–277 (2003).
  CAS PubMed PubMed Central Google Scholar
• Sahai, E. & Marshall, C. J. Differing modes of tumour cell invasion have distinct requirements for Rho/ROCK signalling and extracellular proteolysis. Nature Cell Biol. 5, 711–719 (2003).
  CAS PubMed Google Scholar
• Sanz-Moreno, V. & Marshall, C. J. The plasticity of cytoskeletal dynamics underlying neoplastic cell migration. Curr. Opin. Cell Biol. 22, 690–696 (2010).
  CAS PubMed Google Scholar
• Wolf, K. et al. Multi-step pericellular proteolysis controls the transition from individual to collective cancer cell invasion. Nature Cell Biol. 9, 893–904 (2007).
  CAS PubMed Google Scholar
• Carragher, N. O. et al. Calpain 2 and Src dependence distinguishes mesenchymal and amoeboid modes of tumour cell invasion: a link to integrin function. Oncogene 25, 5726–5740 (2006).
  CAS PubMed Google Scholar
• Carragher, N. O. Calpain inhibition: a therapeutic strategy targeting multiple disease states. Curr. Pharm. Des 12, 615–638 (2006).
  CAS PubMed Google Scholar
• Cortesio, C. L. et al. Calpain 2 and PTP1B function in a novel pathway with Src to regulate invadopodia dynamics and breast cancer cell invasion. J. Cell Biol. 180, 957–971 (2008).
  CAS PubMed PubMed Central Google Scholar
• Vosler, P. S., Brennan, C. S. & Chen, J. Calpain-mediated signaling mechanisms in neuronal injury and neurodegeneration. Mol. Neurobiol. 38, 78–100 (2008).
  CAS PubMed PubMed Central Google Scholar
• Raynaud, F. & Marcilhac, A. Implication of calpain in neuronal apoptosis. A possible regulation of Alzheimer's disease. FEBS J. 273, 3437–3443 (2006).
  CAS PubMed Google Scholar
• Wang, K. K. Calpain and caspase: can you tell the difference? Trends Neurosci. 23, 20–26 (2000).
  PubMed Google Scholar
• Richard, I. et al. Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A. Cell 81, 27–40 (1995). This study identified genetic mutations in calpain 3 as a causative factor in LGMD2A.
  CAS PubMed Google Scholar
• Tan, Y., Wu, C., De Veyra, T. & Greer, P. A. Ubiquitous calpains promote both apoptosis and survival signals in response to different cell death stimuli. J. Biol. Chem. 281, 17689–17698 (2006). An interesting study investigating the role of calpain in apoptosis and survival in response to various stimuli.
  CAS PubMed Google Scholar
• Gonen, H., Shkedy, D., Barnoy, S., Kosower, N. S. & Ciechanover, A. On the involvement of calpains in the degradation of the tumor suppressor protein p53. FEBS Lett. 406, 17–22 (1997).
  CAS PubMed Google Scholar
• Kubbutat, M. H. & Vousden, K. H. Proteolytic cleavage of human p53 by calpain: a potential regulator of protein stability. Mol. Cell. Biol. 17, 460–468 (1997).
  CAS PubMed PubMed Central Google Scholar
• Pariat, M. et al. Proteolysis by calpains: a possible contribution to degradation of p53. Mol. Cell. Biol. 17, 2806–2815 (1997).
  CAS PubMed PubMed Central Google Scholar
• Atencio, I. A., Ramachandra, M., Shabram, P. & Demers, G. W. Calpain inhibitor 1 activates p53-dependent apoptosis in tumor cell lines. Cell Growth Differ. 11, 247–253 (2000).
  CAS PubMed Google Scholar
• Benetti, R. et al. The death substrate Gas2 binds m-calpain and increases susceptibility to p53-dependent apoptosis. EMBO J. 20, 2702–2714 (2001).
  CAS PubMed PubMed Central Google Scholar
• Sedarous, M. et al. Calpains mediate p53 activation and neuronal death evoked by DNA damage. J. Biol. Chem. 278, 26031–26038 (2003).
  CAS PubMed Google Scholar
• Han, Y., Weinman, S., Boldogh, I., Walker, R. K. & Brasier, A. R. Tumor necrosis factor-α-inducible IκBα proteolysis mediated by cytosolic m-calpain. A mechanism parallel to the ubiquitin-proteasome pathway for nuclear factor-κb activation. J. Biol. Chem. 274, 787–794 (1999).
  CAS PubMed Google Scholar
• Pianetti, S., Arsura, M., Romieu-Mourez, R., Coffey, R. J. & Sonenshein, G. E. Her-2/neu overexpression induces NF-κB via a PI3-kinase/Akt pathway involving calpain-mediated degradation of IκB-α that can be inhibited by the tumor suppressor PTEN. Oncogene 20, 1287–1299 (2001). This study implicated that calpain caused NF-κB activation, rather than IκB, following ERBB2 signalling via PI3K and AKT.
  CAS PubMed Google Scholar
• Lee, F. Y. et al. mu-Calpain regulates receptor activator of NF-κB ligand (RANKL)-supported osteoclastogenesis via NF-κB activation in RAW 264.7 cells. J. Biol. Chem. 280, 29929–29936 (2005).
  CAS PubMed Google Scholar
• Shumway, S. D., Maki, M. & Miyamoto, S. The PEST domain of IκBα is necessary and sufficient for in vitro degradation by mu-calpain. J. Biol. Chem. 274, 30874–30881 (1999).
  CAS PubMed Google Scholar
• Baghdiguian, S. et al. Calpain 3 deficiency is associated with myonuclear apoptosis and profound perturbation of the IκB α/NF-κB pathway in limb-girdle muscular dystrophy type 2A. Nature Med. 5, 503–511 (1999).
  CAS PubMed Google Scholar
• Chen, F. et al. Impairment of NF-κB activation and modulation of gene expression by calpastatin. Am. J. Physiol. Cell Physiol. 279, C709–C716 (2000).
  CAS PubMed Google Scholar
• Small, G. W., Chou, T. Y., Dang, C. V. & Orlowski, R. Z. Evidence for involvement of calpain in c-Myc proteolysis in vivo. Arch. Biochem. Biophys. 400, 151–161 (2002).
  CAS PubMed Google Scholar
• Conacci-Sorrell, M., Ngouenet, C. & Eisenman, R. N. Myc-nick: a cytoplasmic cleavage product of Myc that promotes α-tubulin acetylation and cell differentiation. Cell 142, 480–493 (2010). This work demonstrates that calpain can cleave the proto-oncogene Myc to Myc-nick resulting in altered cell morphology.
  CAS PubMed PubMed Central Google Scholar
• Niapour, M., Yu, Y. & Berger, S. A. Regulation of calpain activity by c-Myc through calpastatin and promotion of transformation in c-Myc-negative cells by calpastatin suppression. J. Biol. Chem. 283, 21371–21381 (2008).
  CAS PubMed Google Scholar
• Wang, X. D., Rosales, J. L., Magliocco, A., Gnanakumar, R. & Lee, K. Y. Cyclin E in breast tumors is cleaved into its low molecular weight forms by calpain. Oncogene 22, 769–774 (2003).
  CAS PubMed Google Scholar
• Schollmeyer, J. E. Calpain II involvement in mitosis. Science 240, 911–913 (1988).
  CAS PubMed Google Scholar
• Delmas, C. et al. MAP kinase-dependent degradation of p27Kip1 by calpains in choroidal melanoma cells. Requirement of p27Kip1 nuclear export. J. Biol. Chem. 278, 12443–12451 (2003).
  CAS PubMed Google Scholar
• Bertoli, C., Copetti, T., Lam, E. W., Demarchi, F. & Schneider, C. Calpain small-1 modulates Akt/FoxO3A signaling and apoptosis through PP2A. Oncogene 28, 721–733 (2009).
  CAS PubMed Google Scholar
• Gafni, J., Cong, X., Chen, S. F., Gibson, B. W. & Ellerby, L. M. Calpain-1 cleaves and activates caspase-7. J. Biol. Chem. 284, 25441–25449 (2009). This study demonstrated that calpain could cleave and activate recombinant caspase 7 to produce a distinctly active form of the enzyme.
  CAS PubMed PubMed Central Google Scholar
• Chua, B. T., Guo, K. & Li, P. Direct cleavage by the calcium-activated protease calpain can lead to inactivation of caspases. J. Biol. Chem. 275, 5131–5135 (2000).
  CAS PubMed Google Scholar
• Tan, Y. et al. Ubiquitous calpains promote caspase-12 and JNK activation during endoplasmic reticulum stress-induced apoptosis. J. Biol. Chem. 281, 16016–16024 (2006).
  CAS PubMed Google Scholar
• Martinez, J. A. et al. Calpain and caspase processing of caspase-12 contribute to the ER stress-induced cell death pathway in differentiated PC12 cells. Apoptosis 15, 1480–1493 (2010).
  CAS PubMed Google Scholar
• Barbero, S. et al. Caspase-8 association with the focal adhesion complex promotes tumor cell migration and metastasis. Cancer Res. 69, 3755–3763 (2009).
  CAS PubMed PubMed Central Google Scholar
• Wood, D. E. et al. Bax cleavage is mediated by calpain during drug-induced apoptosis. Oncogene 17, 1069–1078 (1998).
  CAS PubMed Google Scholar
• Gao, G. & Dou, Q. P. N-terminal cleavage of bax by calpain generates a potent proapoptotic 18-kDa fragment that promotes bcl-2-independent cytochrome C release and apoptotic cell death. J. Cell. Biochem. 80, 53–72 (2000).
  CAS PubMed Google Scholar
• Mandic, A. et al. Calpain-mediated Bid cleavage and calpain-independent Bak modulation: two separate pathways in cisplatin-induced apoptosis. Mol. Cell. Biol. 22, 3003–3013 (2002).
  CAS PubMed PubMed Central Google Scholar
• Gil-Parrado, S. et al. Ionomycin-activated calpain triggers apoptosis. A probable role for Bcl-2 family members. J. Biol. Chem. 277, 27217–27226 (2002).
  CAS PubMed Google Scholar
• Li, B. & Dou, Q. P. Bax degradation by the ubiquitin/proteasome-dependent pathway: involvement in tumor survival and progression. Proc. Natl Acad. Sci. USA 97, 3850–3855 (2000).
  CAS PubMed PubMed Central Google Scholar
• Toyota, H. et al. Calpain-induced Bax-cleavage product is a more potent inducer of apoptotic cell death than wild-type Bax. Cancer Lett. 189, 221–230 (2003).
  CAS PubMed Google Scholar
• Lin, L., Ye, Y. & Zakeri, Z. p53, Apaf-1, caspase-3, and -9 are dispensable for Cdk5 activation during cell death. Cell Death Differ. 13, 141–150 (2006).
  PubMed Google Scholar
• Fettucciari, K. et al. Group B Streptococcus induces macrophage apoptosis by calpain activation. J. Immunol. 176, 7542–7556 (2006).
  CAS PubMed Google Scholar
• Hirai, S., Kawasaki, H., Yaniv, M. & Suzuki, K. Degradation of transcription factors, c-Jun and c-Fos, by calpain. FEBS Lett. 287, 57–61 (1991).
  CAS PubMed Google Scholar
• Pariat, M. et al. The sensitivity of c-Jun and c-Fos proteins to calpains depends on conformational determinants of the monomers and not on formation of dimers. Biochem. J. 345, 129–138 (2000).
  CAS PubMed PubMed Central Google Scholar
• Kim, M. J. et al. Calpain-dependent cleavage of cain/cabin1 activates calcineurin to mediate calcium-triggered cell death. Proc. Natl Acad. Sci. USA 99, 9870–9875 (2002).
  CAS PubMed PubMed Central Google Scholar
• Porn-Ares, M. I., Samali, A. & Orrenius, S. Cleavage of the calpain inhibitor, calpastatin, during apoptosis. Cell Death Differ. 5, 1028–1033 (1998).
  CAS PubMed Google Scholar
• Wang, K. K. et al. Caspase-mediated fragmentation of calpain inhibitor protein calpastatin during apoptosis. Arch. Biochem. Biophys. 356, 187–196 (1998).
  CAS PubMed Google Scholar
• Takano, J. et al. Calpain mediates excitotoxic DNA fragmentation via mitochondrial pathways in adult brains: evidence from calpastatin mutant mice. J. Biol. Chem. 280, 16175–16184 (2005).
  CAS PubMed Google Scholar
• Polster, B. M., Basanez, G., Etxebarria, A., Hardwick, J. M. & Nicholls, D. G. Calpain I induces cleavage and release of apoptosis-inducing factor from isolated mitochondria. J. Biol. Chem. 280, 6447–6454 (2005).
  CAS PubMed Google Scholar
• Liu, L., Xing, D. & Chen, W. R. Micro-calpain regulates caspase-dependent and apoptosis inducing factor-mediated caspase-independent apoptotic pathways in cisplatin-induced apoptosis. Int. J. Cancer 125, 2757–2766 (2009).
  CAS PubMed Google Scholar
• Vosler, P. S. et al. Calcium dysregulation induces apoptosis-inducing factor release: cross-talk between PARP-1- and calpain-signaling pathways. Exp. Neurol. 218, 213–220 (2009).
  CAS PubMed PubMed Central Google Scholar
• Mathew, R., Karantza-Wadsworth, V. & White, E. Role of autophagy in cancer. Nature Rev. Cancer 7, 961–967 (2007).
  CAS Google Scholar
• Ravikumar, B. et al. Regulation of mammalian autophagy in physiology and pathophysiology. Physiol. Rev. 90, 1383–1435 (2010).
  CAS PubMed Google Scholar
• Yousefi, S. et al. Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nature Cell Biol. 8, 1124–1132 (2006). This study was one of the first to assess the contribution of calpain to autophagy, showing that calpain-mediated cleavage of ATG5 provoked apoptotic cell death.
  CAS PubMed Google Scholar
• Williams, A. et al. Novel targets for Huntington's disease in an mTOR-independent autophagy pathway. Nature Chem. Biol. 4, 295–305 (2008).
  CAS Google Scholar
• Demarchi, F. et al. Calpain is required for macroautophagy in mammalian cells. J. Cell Biol. 175, 595–605 (2006).
  CAS PubMed PubMed Central Google Scholar
• Cheng, Y. et al. Apoptosis-suppressing and autophagy-promoting effects of calpain on oridonin-induced L929 cell death. Arch. Biochem. Biophys. 475, 148–155 (2008).
  CAS PubMed Google Scholar
• Demarchi, F., Bertoli, C., Greer, P. A. & Schneider, C. Ceramide triggers an NF-κB-dependent survival pathway through calpain. Cell Death Differ. 12, 512–522 (2005).
  CAS PubMed Google Scholar
• Li, C. et al. Proteasome inhibitor PS-341 (bortezomib) induces calpain-dependent IκBα degradation. J. Biol. Chem. 285, 16096–16104 (2010).
  CAS PubMed PubMed Central Google Scholar
• Liu, T. L. et al. Enhancement of chemosensitivity toward peplomycin by calpastatin-stabilized NF-κB p65 in esophageal carcinoma cells: possible involvement of Fas/Fas-L synergism. Apoptosis 11, 1025–1037 (2006).
  CAS PubMed Google Scholar
• Mlynarczuk-Bialy, I. et al. Combined effect of proteasome and calpain inhibition on cisplatin-resistant human melanoma cells. Cancer Res. 66, 7598–7605 (2006).
  CAS PubMed Google Scholar
• Kulkarni, S. et al. Calpain regulates sensitivity to trastuzumab and survival in HER2-positive breast cancer. Oncogene 29, 1339–1350 (2010).
  CAS PubMed Google Scholar
• Pelley, R. P. et al. Calmodulin-androgen receptor (AR) interaction: calcium-dependent, calpain-mediated breakdown of AR in LNCaP prostate cancer cells. Cancer Res. 66, 11754–11762 (2006).
  CAS PubMed Google Scholar
• Chen, H. et al. ERK regulates calpain 2-induced androgen receptor proteolysis in CWR22 relapsed prostate tumor cell lines. J. Biol. Chem. 285, 2368–2374 (2010).
  CAS PubMed Google Scholar
• Libertini, S. J. et al. Evidence for calpain-mediated androgen receptor cleavage as a mechanism for androgen independence. Cancer Res. 67, 9001–9005 (2007).
  CAS PubMed Google Scholar
• Storr, S. J. et al. Calpain-1 expression is associated with relapse-free survival in breast cancer patients treated with trastuzumab following adjuvant chemotherapy. Int. J. Cancer 8 Mar 2011 (doi:10.1002/ijc.25832).
  CAS PubMed Google Scholar
• Del Bello, B., Moretti, D., Gamberucci, A. & Maellaro, E. Cross-talk between calpain and caspase-3/-7 in cisplatin-induced apoptosis of melanoma cells: a major role of calpain inhibition in cell death protection and p53 status. Oncogene 26, 2717–2726 (2007).
  CAS PubMed Google Scholar
• Liu, L. et al. Calpain-mediated pathway dominates cisplatin-induced apoptosis in human lung adenocarcinoma cells as determined by real-time single cell analysis. Int. J. Cancer 122, 2210–2222 (2008).
  CAS PubMed Google Scholar
• Donkor, I. O. A survey of calpain inhibitors. Curr. Med. Chem. 7, 1171–1188 (2000).
  CAS PubMed Google Scholar
• Todd, B. et al. A structural model for the inhibition of calpain by calpastatin: crystal structures of the native domain VI of calpain and its complexes with calpastatin peptide and a small molecule inhibitor. J. Mol. Biol. 328, 131–146 (2003).
  CAS PubMed Google Scholar
• Wang, K. K. et al. An α-mercaptoacrylic acid derivative is a selective nonpeptide cell-permeable calpain inhibitor and is neuroprotective. Proc. Natl Acad. Sci. USA 93, 6687–6692 (1996).
  CAS PubMed PubMed Central Google Scholar
• Graybill, T. L. et al. Inhibition of human erythrocyte calpain-I by novel quinoline carboxamides. Bioorg. Med. Chem. Lett. 5, 387–392 (1995).
  CAS Google Scholar
• Zatz, M. & Starling, A. Calpains and disease. N. Engl. J. Med. 352, 2413–2423 (2005).
  CAS PubMed Google Scholar
• Biswas, S., Harris, F., Dennison, S., Singh, J. & Phoenix, D. A. Calpains: targets of cataract prevention? Trends Mol. Med. 10, 78–84 (2004).
  CAS PubMed Google Scholar
• Shields, D. C., Schaecher, K. E., Saido, T. C. & Banik, N. L. A putative mechanism of demyelination in multiple sclerosis by a proteolytic enzyme, calpain. Proc. Natl Acad. Sci. USA 96, 11486–11491 (1999).
  CAS PubMed PubMed Central Google Scholar
• Mani, S. K. et al. Calpain inhibition preserves myocardial structure and function following myocardial infarction. Am. J. Physiol. Heart Circ. Physiol. 297, H1744–H1751 (2009).
  CAS PubMed PubMed Central Google Scholar
• Horikawa, Y. et al. Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. Nature Genet. 26, 163–175 (2000).
  CAS PubMed Google Scholar
• Saez, M. E. et al. Calpain-5 gene variants are associated with diastolic blood pressure and cholesterol levels. BMC Med. Genet. 8, 1 (2007).
  PubMed PubMed Central Google Scholar
• Gonzalez, A. et al. Specific haplotypes of the CALPAIN-5 gene are associated with polycystic ovary syndrome. Hum. Reprod. 21, 943–951 (2006).
  CAS PubMed Google Scholar
• Penna, I., Du, H., Ferriani, R. & Taylor, H. S. Calpain5 expression is decreased in endometriosis and regulated by HOXA10 in human endometrial cells. Mol. Hum. Reprod. 14, 613–618 (2008).
  CAS PubMed PubMed Central Google Scholar
• Kerbiriou, M., Teng, L., Benz, N., Trouve, P. & Ferec, C. The calpain, caspase 12, caspase 3 cascade leading to apoptosis is altered in F508del-CFTR expressing cells. PLoS ONE 4, e8436 (2009).
  PubMed PubMed Central Google Scholar