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Gene Review

Cast  -  calpastatin

Mus musculus

Synonyms: Calpain inhibitor, Calpastatin
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Disease relevance of Cast


High impact information on Cast

  • Transplanted long-term cultured pre-BI cells expressing calpastatin are resistant to B cell receptor-induced apoptosis [6].
  • Furthermore, calpain activation is associated with decreased expression levels of calpastatin, which is upregulated by CD40 ligation [7].
  • Whereas wild-type cells extend lamellae within 30 min after plating, all of the calpastatin-overexpressing cell lines fail to spread and assemble actin-rich processes [8].
  • The calpain inhibitor calpeptin increased WASP levels in activated T and B cells from the WASP patients, but not in primary T cells from the patients or from WIP(-/-) mice [9].
  • N-acetyl-Leu-Leu-norleucinal, or overexpression of calpastatin, inhibits reporter gene expression mediated by the C/EBPalpha gene promoter by preventing C/EBPbeta, a transcriptional activator of the C/EBPalpha gene, from binding to the promoter [10].

Chemical compound and disease context of Cast


Biological context of Cast


Anatomical context of Cast

  • Regulation of calpain activity by calpastatin thus provides a mechanism for regulating the anchoring of basal bodies to the apical cytoskeleton in ciliated cells [16].
  • RNase protection confirmed the decrease in calpastatin expression and decreased calpastatin was detected in the proximal pulmonary epithelium of foxj1(-/-) mice by immunohistochemistry [16].
  • Many studies have demonstrated that the calcium-dependent proteolytic system (calpains and calpastatin) is involved in myoblast differentiation [17].
  • In the present experiments, using a mouse muscle cell line (C2C12) we have analyzed both the sequences of appearance and the expression profiles of calpains 1, 2, 3 and calpastatin during the course of myoblast differentiation [17].
  • Exposure of preadipocytes to the calpain inhibitor N-acetyl-Leu-Leu-norleucinal or overexpression of calpastatin, a specific endogenous inhibitor of calpain, blocks expression of adipocyte-specific genes, notably the CCAAT/enhancer-binding protein (C/EBP)alpha gene, and acquisition of the adipocyte phenotype [10].

Associations of Cast with chemical compounds


Physical interactions of Cast


Regulatory relationships of Cast


Other interactions of Cast


Analytical, diagnostic and therapeutic context of Cast


  1. Calpain activation and secretion promote glomerular injury in experimental glomerulonephritis: evidence from calpastatin-transgenic mice. Peltier, J., Bellocq, A., Perez, J., Doublier, S., Dubois, Y.C., Haymann, J.P., Camussi, G., Baud, L. J. Am. Soc. Nephrol. (2006) [Pubmed]
  2. Activation of calpains, calpastatin and spectrin cleavage in the brain during the pathology of fatal murine cerebral malaria. Shukla, M., Rajgopal, Y., Babu, P.P. Neurochem. Int. (2006) [Pubmed]
  3. Novel mechanisms of target cell death and survival and of therapeutic action of IVIg in Pemphigus. Arredondo, J., Chernyavsky, A.I., Karaouni, A., Grando, S.A. Am. J. Pathol. (2005) [Pubmed]
  4. The novel calpain inhibitor SJA6017 improves functional outcome after delayed administration in a mouse model of diffuse brain injury. Kupina, N.C., Nath, R., Bernath, E.E., Inoue, J., Mitsuyoshi, A., Yuen, P.W., Wang, K.K., Hall, E.D. J. Neurotrauma (2001) [Pubmed]
  5. Insulin-like growth factor-I and high protein diet decrease calpain-mediated proteolysis in murine muscular dystrophy. Wingertzahn, M.A., Zdanowicz, M.M., Slonim, A.E. Proc. Soc. Exp. Biol. Med. (1998) [Pubmed]
  6. Transplanted long-term cultured pre-BI cells expressing calpastatin are resistant to B cell receptor-induced apoptosis. Ruiz-Vela, A., Serrano, F., González, M.A., Abad, J.L., Bernad, A., Maki, M., Martínez-A, C. J. Exp. Med. (2001) [Pubmed]
  7. Implication of calpain in caspase activation during B cell clonal deletion. Ruiz-Vela, A., González de Buitrago, G., Martínez-A, C. EMBO J. (1999) [Pubmed]
  8. Calpain regulates actin remodeling during cell spreading. Potter, D.A., Tirnauer, J.S., Janssen, R., Croall, D.E., Hughes, C.N., Fiacco, K.A., Mier, J.W., Maki, M., Herman, I.M. J. Cell Biol. (1998) [Pubmed]
  9. WIP is a chaperone for Wiskott-Aldrich syndrome protein (WASP). de la Fuente, M.A., Sasahara, Y., Calamito, M., Antón, I.M., Elkhal, A., Gallego, M.D., Suresh, K., Siminovitch, K., Ochs, H.D., Anderson, K.C., Rosen, F.S., Geha, R.S., Ramesh, N. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  10. Role of calpain in adipocyte differentiation. Patel, Y.M., Lane, M.D. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  11. Calpeptin suppresses tumor necrosis factor-alpha-induced death and accumulation of p53 in L929 mouse sarcoma cells. Kim, B.J., Jung, Y.K. Apoptosis (2002) [Pubmed]
  12. Overexpression of a calpastatin transgene in mdx muscle reduces dystrophic pathology. Spencer, M.J., Mellgren, R.L. Hum. Mol. Genet. (2002) [Pubmed]
  13. Calpain mediates excitotoxic DNA fragmentation via mitochondrial pathways in adult brains: evidence from calpastatin mutant mice. Takano, J., Tomioka, M., Tsubuki, S., Higuchi, M., Iwata, N., Itohara, S., Maki, M., Saido, T.C. J. Biol. Chem. (2005) [Pubmed]
  14. Possible regulation of the conventional calpain system by skeletal muscle-specific calpain, p94/calpain 3. Ono, Y., Kakinuma, K., Torii, F., Irie, A., Nakagawa, K., Labeit, S., Abe, K., Suzuki, K., Sorimachi, H. J. Biol. Chem. (2004) [Pubmed]
  15. The calpain-calpastatin system and cellular proliferation and differentiation in rodent osteoblastic cells. Murray, S.S., Grisanti, M.S., Bentley, G.V., Kahn, A.J., Urist, M.R., Murray, E.J. Exp. Cell Res. (1997) [Pubmed]
  16. Foxj1 regulates basal body anchoring to the cytoskeleton of ciliated pulmonary epithelial cells. Gomperts, B.N., Gong-Cooper, X., Hackett, B.P. J. Cell. Sci. (2004) [Pubmed]
  17. Characterization of the calcium-dependent proteolytic system in a mouse muscle cell line. Dargelos, E., Dedieu, S., Moyen, C., Poussard, S., Veschambre, P., Brustis, J.J., Cottin, P. Mol. Cell. Biochem. (2002) [Pubmed]
  18. Distinct mechanistic roles of calpain and caspase activation in neurodegeneration as revealed in mice overexpressing their specific inhibitors. Higuchi, M., Tomioka, M., Takano, J., Shirotani, K., Iwata, N., Masumoto, H., Maki, M., Itohara, S., Saido, T.C. J. Biol. Chem. (2005) [Pubmed]
  19. Calpain and calpastatin regulate neutrophil apoptosis. Squier, M.K., Sehnert, A.J., Sellins, K.S., Malkinson, A.M., Takano, E., Cohen, J.J. J. Cell. Physiol. (1999) [Pubmed]
  20. Calpain inhibitors delay injury-induced apoptosis in adult mouse spinal cord motor neurons. Momeni, H.R., Kanje, M. Neuroreport (2006) [Pubmed]
  21. Participation of the conventional calpains in apoptosis. Lu, T., Xu, Y., Mericle, M.T., Mellgren, R.L. Biochim. Biophys. Acta (2002) [Pubmed]
  22. Protective effect of type 2 diabetes on acetaminophen-induced hepatotoxicity in male Swiss-Webster mice. Sawant, S.P., Dnyanmote, A.V., Mitra, M.S., Chilakapati, J., Warbritton, A., Latendresse, J.R., Mehendale, H.M. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  23. Calpain, an upstream regulator of thymocyte apoptosis. Squier, M.K., Cohen, J.J. J. Immunol. (1997) [Pubmed]
  24. Enhanced proteolysis of IkappaBalpha and IkappaBbeta proteins in astrocytes by Moloney murine leukemia virus (MoMuLV)-ts1 infection: a potential mechanism of NF-kappaB activation. Kim, H.T., Qiang, W., Wong, P.K., Stoica, G. J. Neurovirol. (2001) [Pubmed]
  25. Lp82 is the dominant form of calpain in young mouse lens. Ma, H., Hata, I., Shih, M., Fukiage, C., Nakamura, Y., Azuma, M., Shearer, T.R. Exp. Eye Res. (1999) [Pubmed]
  26. The insulin-induced down-regulation of IRS-1 in 3T3-L1 adipocytes is mediated by a calcium-dependent thiol protease. Smith, L.K., Rice, K.M., Garner, C.W. Mol. Cell. Endocrinol. (1996) [Pubmed]
  27. Parathyroid hormone-induced retraction of MC3T3-E1 osteoblastic cells is attenuated by the calpain inhibitor N-Ac-Leu-Leu-norleucinal. Murray, E.J., Tram, K.K., Murray, S.S., Lee, D.B. Metab. Clin. Exp. (1995) [Pubmed]
  28. Myoblast migration is regulated by calpain through its involvement in cell attachment and cytoskeletal organization. Dedieu, S., Poussard, S., Mazères, G., Grise, F., Dargelos, E., Cottin, P., Brustis, J.J. Exp. Cell Res. (2004) [Pubmed]
  29. Calpain contributes to silica-induced I kappa B-alpha degradation and nuclear factor-kappa B activation. Chen, F., Lu, Y., Kuhn, D.C., Maki, M., Shi, X., Sun, S.C., Demers, L.M. Arch. Biochem. Biophys. (1997) [Pubmed]
  30. Stretch-induced nitric oxide modulates mechanical properties of skeletal muscle cells. Zhang, J.S., Kraus, W.E., Truskey, G.A. Am. J. Physiol., Cell Physiol. (2004) [Pubmed]
  31. Altered gene expression for calpain/calpastatin system in motor neuron degeneration (Mnd) mutant mouse brain and spinal cord. Li, J., Nixon, R., Messer, A., Berman, S., Bursztajn, S. Brain Res. Mol. Brain Res. (1998) [Pubmed]
  32. Structure of mouse calpastatin isoforms: implications of species-common and species-specific alternative splicing. Takano, J., Kawamura, T., Murase, M., Hitomi, K., Maki, M. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  33. Multiple forms of rat calpastatin cDNA in the coding region of functionally unknown amino-terminal domain. Lee, W.J., Hatanaka, M., Maki, M. Biochim. Biophys. Acta (1992) [Pubmed]
  34. Calpain is activated in degenerating photoreceptors in the rd1 mouse. Paquet-Durand, F., Azadi, S., Hauck, S.M., Ueffing, M., van Veen, T., Ekström, P. J. Neurochem. (2006) [Pubmed]
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