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Gene Review

Casp3  -  caspase 3

Mus musculus

Synonyms: A830040C14Rik, AC-3, Apopain, CASP-3, CC3, ...
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Disease relevance of Casp3


Psychiatry related information on Casp3


High impact information on Casp3

  • Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal [12].
  • Further analysis showed that lysophosphatidylcholine was released from apoptotic cells due to the caspase-3 mediated activation of the calcium-independent phospholipase A(2) [12].
  • As compared to cell lines established from wild-type embryos, cells lacking cytochrome c show reduced caspase-3 activation and are resistant to the proapoptotic effects of UV irradiation, serum withdrawal, or staurosporine [13].
  • Comparison of the requirement for Casp9 and Casp3 in different apoptotic settings indicates the existence of at least four different apoptotic pathways in mammalian cells [14].
  • Pml is required for caspase 1 and caspase 3 activation upon exposure to these stimuli [15].

Chemical compound and disease context of Casp3


Biological context of Casp3


Anatomical context of Casp3


Associations of Casp3 with chemical compounds


Physical interactions of Casp3


Enzymatic interactions of Casp3


Regulatory relationships of Casp3


Other interactions of Casp3

  • However, when compared with normal control cells, Apaf-1(-/-) or caspase-3(-/-) cells fail to exhibit oligonucleosomal chromatin digestion and a more advanced pattern of chromatin condensation (stage II) [41].
  • At day 1 after weaning, high levels of both Fas and FasL proteins and caspase 3 were observed and coincided with the appearance of apoptotic cells in ducts and glands [42].
  • The data therefore support the existence of a fully implemented apoptotic pathway initiated by GrB, propagated by caspase-3, and perpetuated by a mitochondrial amplification loop but also emphasize the presence of an ancillary caspase-dependent, mitochondria-independent pathway [43].
  • We show that GT induces apoptotic cell death by activating the proapoptotic Bcl-2 family member Bak, but not Bax, to elicit the generation of reactive oxygen species, the mitochondrial release of apoptogenic factors, and caspase-3 activation [44].
  • We demonstrate here that in addition to its defect in cytokine maturation, caspase-11-deficient mice have a reduced number of apoptotic cells and a defect in caspase-3 activation after middle cerebral artery occlusion (MCAO), a mouse model of stroke [45].

Analytical, diagnostic and therapeutic context of Casp3


  1. Clusterin contributes to caspase-3-independent brain injury following neonatal hypoxia-ischemia. Han, B.H., DeMattos, R.B., Dugan, L.L., Kim-Han, J.S., Brendza, R.P., Fryer, J.D., Kierson, M., Cirrito, J., Quick, K., Harmony, J.A., Aronow, B.J., Holtzman, D.M. Nat. Med. (2001) [Pubmed]
  2. Caspase activation and neuroprotection in caspase-3- deficient mice after in vivo cerebral ischemia and in vitro oxygen glucose deprivation. Le, D.A., Wu, Y., Huang, Z., Matsushita, K., Plesnila, N., Augustinack, J.C., Hyman, B.T., Yuan, J., Kuida, K., Flavell, R.A., Moskowitz, M.A. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  3. Caspase-3-dependent beta-cell apoptosis in the initiation of autoimmune diabetes mellitus. Liadis, N., Murakami, K., Eweida, M., Elford, A.R., Sheu, L., Gaisano, H.Y., Hakem, R., Ohashi, P.S., Woo, M. Mol. Cell. Biol. (2005) [Pubmed]
  4. Ischemic preconditioning protects the mouse liver by inhibition of apoptosis through a caspase-dependent pathway. Yadav, S.S., Sindram, D., Perry, D.K., Clavien, P.A. Hepatology (1999) [Pubmed]
  5. Deficiency in DNA polymerase beta provokes replication-dependent apoptosis via DNA breakage, Bcl-2 decline and caspase-3/9 activation. Ochs, K., Lips, J., Profittlich, S., Kaina, B. Cancer Res. (2002) [Pubmed]
  6. Caspase 3-dependent cell death of neurons contributes to the pathogenesis of West Nile virus encephalitis. Samuel, M.A., Morrey, J.D., Diamond, M.S. J. Virol. (2007) [Pubmed]
  7. Neuroprotective and neurotrophic actions of the mood stabilizer lithium: can it be used to treat neurodegenerative diseases? Chuang, D.M. Critical reviews in neurobiology. (2004) [Pubmed]
  8. Synaptic pathology and cell death in the cerebellum in Creutzfeldt-Jakob disease. Ferrer, I. Cerebellum (2002) [Pubmed]
  9. Hepatitis B virus X protein sensitizes primary mouse hepatocytes to ethanol- and TNF-alpha-induced apoptosis by a caspase-3-dependent mechanism. Kim, W.H., Hong, F., Jaruga, B., Zhang, Z.S., Fan, S.J., Liang, T.J., Gao, B. Cell. Mol. Immunol. (2005) [Pubmed]
  10. Critical period for sensory experience-dependent survival of newly generated granule cells in the adult mouse olfactory bulb. Yamaguchi, M., Mori, K. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  11. Caspase-3-mediated cleavage of PHF-1 tau during apoptosis irrespective of excitotoxicity and oxidative stress: an implication to Alzheimer's disease. Kang, H.J., Yoon, W.J., Moon, G.J., Kim, D.Y., Sohn, S., Kwon, H.J., Gwag, B.J. Neurobiol. Dis. (2005) [Pubmed]
  12. Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Lauber, K., Bohn, E., Kröber, S.M., Xiao, Y.J., Blumenthal, S.G., Lindemann, R.K., Marini, P., Wiedig, C., Zobywalski, A., Baksh, S., Xu, Y., Autenrieth, I.B., Schulze-Osthoff, K., Belka, C., Stuhler, G., Wesselborg, S. Cell (2003) [Pubmed]
  13. Cytochrome c deficiency causes embryonic lethality and attenuates stress-induced apoptosis. Li, K., Li, Y., Shelton, J.M., Richardson, J.A., Spencer, E., Chen, Z.J., Wang, X., Williams, R.S. Cell (2000) [Pubmed]
  14. Differential requirement for caspase 9 in apoptotic pathways in vivo. Hakem, R., Hakem, A., Duncan, G.S., Henderson, J.T., Woo, M., Soengas, M.S., Elia, A., de la Pompa, J.L., Kagi, D., Khoo, W., Potter, J., Yoshida, R., Kaufman, S.A., Lowe, S.W., Penninger, J.M., Mak, T.W. Cell (1998) [Pubmed]
  15. PML is essential for multiple apoptotic pathways. Wang, Z.G., Ruggero, D., Ronchetti, S., Zhong, S., Gaboli, M., Rivi, R., Pandolfi, P.P. Nat. Genet. (1998) [Pubmed]
  16. Activation of caspase 3 (CPP32)-like proteases is essential for TNF-alpha-induced hepatic parenchymal cell apoptosis and neutrophil-mediated necrosis in a murine endotoxin shock model. Jaeschke, H., Fisher, M.A., Lawson, J.A., Simmons, C.A., Farhood, A., Jones, D.A. J. Immunol. (1998) [Pubmed]
  17. Potential role of caspase-3 and -9 in arsenic trioxide-mediated apoptosis in PCI-1 head and neck cancer cells. Seol, J.G., Park, W.H., Kim, E.S., Jung, C.W., Hyun, J.M., Lee, Y.Y., Kim, B.K. Int. J. Oncol. (2001) [Pubmed]
  18. Paraoxon induces apoptosis in EL4 cells via activation of mitochondrial pathways. Saleh, A.M., Vijayasarathy, C., Masoud, L., Kumar, L., Shahin, A., Kambal, A. Toxicol. Appl. Pharmacol. (2003) [Pubmed]
  19. Hypoxia induces apoptosis by caspase activation accompanying cytochrome C release from mitochondria in MC3T3E1 osteoblasts. p38 MAPK is related in hypoxia-induced apoptosis. Chae, H.J., Kim, S.C., Han, K.S., Chae, S.W., An, N.H., Kim, H.M., Kim, H.H., Lee, Z.H., Kim, H.R. Immunopharmacology and immunotoxicology. (2001) [Pubmed]
  20. Caspase-3-generated fragment of gelsolin: effector of morphological change in apoptosis. Kothakota, S., Azuma, T., Reinhard, C., Klippel, A., Tang, J., Chu, K., McGarry, T.J., Kirschner, M.W., Koths, K., Kwiatkowski, D.J., Williams, L.T. Science (1997) [Pubmed]
  21. Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes. Woo, M., Hakem, R., Soengas, M.S., Duncan, G.S., Shahinian, A., Kägi, D., Hakem, A., McCurrach, M., Khoo, W., Kaufman, S.A., Senaldi, G., Howard, T., Lowe, S.W., Mak, T.W. Genes Dev. (1998) [Pubmed]
  22. Caspase-3 regulates cell cycle in B cells: a consequence of substrate specificity. Woo, M., Hakem, R., Furlonger, C., Hakem, A., Duncan, G.S., Sasaki, T., Bouchard, D., Lu, L., Wu, G.E., Paige, C.J., Mak, T.W. Nat. Immunol. (2003) [Pubmed]
  23. Caspase-3 controls both cytoplasmic and nuclear events associated with Fas-mediated apoptosis in vivo. Zheng, T.S., Schlosser, S.F., Dao, T., Hingorani, R., Crispe, I.N., Boyer, J.L., Flavell, R.A. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  24. Deficiency in caspase-9 or caspase-3 induces compensatory caspase activation. Zheng, T.S., Hunot, S., Kuida, K., Momoi, T., Srinivasan, A., Nicholson, D.W., Lazebnik, Y., Flavell, R.A. Nat. Med. (2000) [Pubmed]
  25. Alcohol increases tumor necrosis factor alpha and decreases nuclear factor-kappab to activate hepatic apoptosis in genetically obese mice. Robin, M.A., Demeilliers, C., Sutton, A., Paradis, V., Maisonneuve, C., Dubois, S., Poirel, O., Lettéron, P., Pessayre, D., Fromenty, B. Hepatology (2005) [Pubmed]
  26. Failure of activation of caspase-9 induces a higher threshold for apoptosis and cisplatin resistance in testicular cancer. Mueller, T., Voigt, W., Simon, H., Fruehauf, A., Bulankin, A., Grothey, A., Schmoll, H.J. Cancer Res. (2003) [Pubmed]
  27. Silibinin protects against photocarcinogenesis via modulation of cell cycle regulators, mitogen-activated protein kinases, and Akt signaling. Mallikarjuna, G., Dhanalakshmi, S., Singh, R.P., Agarwal, C., Agarwal, R. Cancer Res. (2004) [Pubmed]
  28. Expression of a murine homologue of the inhibitor of apoptosis protein is related to cell proliferation. Kobayashi, K., Hatano, M., Otaki, M., Ogasawara, T., Tokuhisa, T. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  29. Formation of noncanonical high molecular weight caspase-3 and -6 complexes and activation of caspase-12 during serum starvation induced apoptosis in AKR-2B mouse fibroblasts. Kilic, M., Schäfer, R., Hoppe, J., Kagerhuber, U. Cell Death Differ. (2002) [Pubmed]
  30. HPMA copolymers containing doxorubicin bound by a proteolytically or hydrolytically cleavable bond: comparison of biological properties in vitro. Kovár, M., Kovár, L., Subr, V., Etrych, T., Ulbrich, K., Mrkvan, T., Loucká, J., Ríhová, B. Journal of controlled release : official journal of the Controlled Release Society. (2004) [Pubmed]
  31. Gelsolin in complex with phosphatidylinositol 4,5-bisphosphate inhibits caspase-3 and -9 to retard apoptotic progression. Azuma, T., Koths, K., Flanagan, L., Kwiatkowski, D. J. Biol. Chem. (2000) [Pubmed]
  32. The gamma subunit of the rod photoreceptor cGMP phosphodiesterase can modulate the proteolysis of two cGMP binding cGMP-specific phosphodiesterases (PDE6 and PDE5) by caspase-3. Frame, M., Wan, K.F., Tate, R., Vandenabeele, P., Pyne, N.J. Cell. Signal. (2001) [Pubmed]
  33. Nuclear localization of procaspase-9 and processing by a caspase-3-like activity in mammary epithelial cells. Ritter, P.M., Marti, A., Blanc, C., Baltzer, A., Krajewski, S., Reed, J.C., Jaggi, R. Eur. J. Cell Biol. (2000) [Pubmed]
  34. PKCdelta alternatively spliced isoforms modulate cellular apoptosis in retinoic acid-induced differentiation of human NT2 cells and mouse embryonic stem cells. Patel, N.A., Song, S.S., Cooper, D.R. Gene Expr. (2006) [Pubmed]
  35. Akt1/Akt2 and mammalian target of rapamycin/Bim play critical roles in osteoclast differentiation and survival, respectively, whereas Akt is dispensable for cell survival in isolated osteoclast precursors. Sugatani, T., Hruska, K.A. J. Biol. Chem. (2005) [Pubmed]
  36. Acceleration of apoptotic cell death after the cleavage of Bcl-XL protein by caspase-3-like proteases. Fujita, N., Nagahashi, A., Nagashima, K., Rokudai, S., Tsuruo, T. Oncogene (1998) [Pubmed]
  37. Regulation of caspase 9 through phosphorylation by protein kinase C zeta in response to hyperosmotic stress. Brady, S.C., Allan, L.A., Clarke, P.R. Mol. Cell. Biol. (2005) [Pubmed]
  38. Perforin-dependent activation-induced cell death acts through caspase 3 but not through caspases 8 or 9. Chen, L., Woo, M., Hakem, R., Miller, R.G. Eur. J. Immunol. (2003) [Pubmed]
  39. Protective effect of cyclosporin A and FK506 from nitric oxide-dependent apoptosis in activated macrophages. Hortelano, S., López-Collazo, E., Boscá, L. Br. J. Pharmacol. (1999) [Pubmed]
  40. Induction of competing apoptotic and survival signaling pathways in the macrophage by the ribotoxic trichothecene deoxynivalenol. Zhou, H.R., Islam, Z., Pestka, J.J. Toxicol. Sci. (2005) [Pubmed]
  41. Two distinct pathways leading to nuclear apoptosis. Susin, S.A., Daugas, E., Ravagnan, L., Samejima, K., Zamzami, N., Loeffler, M., Costantini, P., Ferri, K.F., Irinopoulou, T., Prévost, M.C., Brothers, G., Mak, T.W., Penninger, J., Earnshaw, W.C., Kroemer, G. J. Exp. Med. (2000) [Pubmed]
  42. Roles of Fas and Fas ligand during mammary gland remodeling. Song, J., Sapi, E., Brown, W., Nilsen, J., Tartaro, K., Kacinski, B.M., Craft, J., Naftolin, F., Mor, G. J. Clin. Invest. (2000) [Pubmed]
  43. Granzyme B activates procaspase-3 which signals a mitochondrial amplification loop for maximal apoptosis. Metkar, S.S., Wang, B., Ebbs, M.L., Kim, J.H., Lee, Y.J., Raja, S.M., Froelich, C.J. J. Cell Biol. (2003) [Pubmed]
  44. The mitochondrial protein Bak is pivotal for gliotoxin-induced apoptosis and a critical host factor of Aspergillus fumigatus virulence in mice. Pardo, J., Urban, C., Galvez, E.M., Ekert, P.G., Müller, U., Kwon-Chung, J., Lobigs, M., Müllbacher, A., Wallich, R., Borner, C., Simon, M.M. J. Cell Biol. (2006) [Pubmed]
  45. Dual role of caspase-11 in mediating activation of caspase-1 and caspase-3 under pathological conditions. Kang, S.J., Wang, S., Hara, H., Peterson, E.P., Namura, S., Amin-Hanjani, S., Huang, Z., Srinivasan, A., Tomaselli, K.J., Thornberry, N.A., Moskowitz, M.A., Yuan, J. J. Cell Biol. (2000) [Pubmed]
  46. GDNF availability determines enteric neuron number by controlling precursor proliferation. Gianino, S., Grider, J.R., Cresswell, J., Enomoto, H., Heuckeroth, R.O. Development (2003) [Pubmed]
  47. Elevated proapoptotic Bax and caspase 3 activation in the NOD.scid model of Sjögren's syndrome. Masago, R., Aiba-Masago, S., Talal, N., Zuluaga, F.J., Al-Hashimi, I., Moody, M., Lau, C.A., Peck, A.B., Brayer, J., Humphreys-Beher, M.G., Dang, H. Arthritis Rheum. (2001) [Pubmed]
  48. IL-1 beta convertase (ICE) does not play a requisite role in apoptosis induced in T lymphoblasts by Fas-dependent or Fas-independent CTL effector mechanisms. Smith, D.J., McGuire, M.J., Tocci, M.J., Thiele, D.L. J. Immunol. (1997) [Pubmed]
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