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Gene Review

Casp2  -  caspase 2

Mus musculus

Synonyms: CASP-2, Caspase-2, ICH-1, Ich-1, Ich1, ...
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Disease relevance of Casp2


High impact information on Casp2


Chemical compound and disease context of Casp2

  • We have compared the behavior of wild-type mouse NEDD-2, a neural precursor cell-expressed, developmentally down-regulated cysteine protease gene, to various mutant forms of the gene in both apoptotic activity in neuronal cells and proteolytic cleavage in the Semliki Forest virus and rabbit reticulocyte protein expression systems [10].

Biological context of Casp2


Anatomical context of Casp2


Associations of Casp2 with chemical compounds

  • Caspase-2 and -3 that were predominantly activated in response to cisplatin provided a unique model to study the role of these caspases in AIF release [15].
  • In all of the neuronal populations studied here (hippocampal neurons, sympathetic neurons, and PC12 cells), cell death was blocked by the broad spectrum caspase inhibitor N-benzyloxycarbonyl-val-ala-asp-fluoromethyl ketone and more specifically by the downregulation of caspase-2 with antisense oligonucleotides [3].
  • These data suggest sequential initiator caspase-2 and caspase-8 activation in the mitochondrial apoptotic pathway induced by ceramide or etoposide [18].
  • BACKGROUND: The Nedd2/Ich-1 protein belongs to a growing family of mammalian cysteine proteases similar to interleukin-1 beta converting enzyme (ICE) [19].
  • Both poly-(ADP ribose) polymerase and pro-ICE and Ced-3 homolog-1 (ICH-1) appear to be cleaved in a BAF-inhibitable manner, although the majority of pro-CPP32 appears unchanged, suggesting that ICH-1 is activated during neuronal PCD [20].

Regulatory relationships of Casp2

  • The caspase-2 prodomain also regulates caspase-2 activity via a caspase recruitment domain that mediates oligomerization of procaspase-2 molecules and their subsequent autoactivation [13].
  • The data are consistent with a model in which Caspase-2 induces apoptosis via cleavage of Bid at D59 and the subsequent engagement of the mitochondrial (intrinsic) pathway [21].
  • PKCdelta was cleaved/activated in a caspase-2-dependent manner after doxorubicin treatment both in cells and in vitro [22].

Other interactions of Casp2

  • Procaspase-2 was maturated by caspase-8 and -3, and to a lesser extent by caspase-7, while the active caspase-2 did not process any of the procaspases examined, except its own precursor [23].
  • Caspase-2 activation was a critical response from p53, which was markedly induced and phosphorylated in cisplatin-treated cells [15].
  • This approach unambiguously identifies the apical caspase activated in response to apoptotic stimuli, and establishes caspase-2 as a proximal mediator of heat shock-induced apoptosis [11].
  • This activation of caspase-2 was also observed in cells protected from heat-shock-induced apoptosis by Bcl-2 or Bcl-xL [11].
  • We provide evidence that PIDD-induced cell death is associated with the early activation of caspase-2 and later activation of caspase-3 and -7 [12].

Analytical, diagnostic and therapeutic context of Casp2


  1. Caspase-2 triggers Bax-Bak-dependent and -independent cell death in colon cancer cells treated with resveratrol. Mohan, J., Gandhi, A.A., Bhavya, B.C., Rashmi, R., Karunagaran, D., Indu, R., Santhoshkumar, T.R. J. Biol. Chem. (2006) [Pubmed]
  2. Gustatory innervation and bax-dependent caspase-2: participants in the life and death pathways of mouse taste receptor cells. Zeng, Q., Kwan, A., Oakley, B. J. Comp. Neurol. (2000) [Pubmed]
  3. Caspase-2 mediates neuronal cell death induced by beta-amyloid. Troy, C.M., Rabacchi, S.A., Friedman, W.J., Frappier, T.F., Brown, K., Shelanski, M.L. J. Neurosci. (2000) [Pubmed]
  4. Induction of apoptosis by the mouse Nedd2 gene, which encodes a protein similar to the product of the Caenorhabditis elegans cell death gene ced-3 and the mammalian IL-1 beta-converting enzyme. Kumar, S., Kinoshita, M., Noda, M., Copeland, N.G., Jenkins, N.A. Genes Dev. (1994) [Pubmed]
  5. Salmonella-induced caspase-2 activation in macrophages: a novel mechanism in pathogen-mediated apoptosis. Jesenberger, V., Procyk, K.J., Yuan, J., Reipert, S., Baccarini, M. J. Exp. Med. (2000) [Pubmed]
  6. Metabolic regulation of oocyte cell death through the CaMKII-mediated phosphorylation of caspase-2. Nutt, L.K., Margolis, S.S., Jensen, M., Herman, C.E., Dunphy, W.G., Rathmell, J.C., Kornbluth, S. Cell (2005) [Pubmed]
  7. Mice deficient in IL-1 beta-converting enzyme are defective in production of mature IL-1 beta and resistant to endotoxic shock. Li, P., Allen, H., Banerjee, S., Franklin, S., Herzog, L., Johnston, C., McDowell, J., Paskind, M., Rodman, L., Salfeld, J. Cell (1995) [Pubmed]
  8. Ich-1, an Ice/ced-3-related gene, encodes both positive and negative regulators of programmed cell death. Wang, L., Miura, M., Bergeron, L., Zhu, H., Yuan, J. Cell (1994) [Pubmed]
  9. Sequential activation of ICE-like and CPP32-like proteases during Fas-mediated apoptosis. Enari, M., Talanian, R.V., Wong, W.W., Nagata, S. Nature (1996) [Pubmed]
  10. Dissecting processing and apoptotic activity of a cysteine protease by mutant analysis. Allet, B., Hochmann, A., Martinou, I., Berger, A., Missotten, M., Antonsson, B., Sadoul, R., Martinou, J.C., Bernasconi, L. J. Cell Biol. (1996) [Pubmed]
  11. In situ trapping of activated initiator caspases reveals a role for caspase-2 in heat shock-induced apoptosis. Tu, S., McStay, G.P., Boucher, L.M., Mak, T., Beere, H.M., Green, D.R. Nat. Cell Biol. (2006) [Pubmed]
  12. Apoptosis caused by p53-induced protein with death domain (PIDD) depends on the death adapter protein RAIDD. Berube, C., Boucher, L.M., Ma, W., Wakeham, A., Salmena, L., Hakem, R., Yeh, W.C., Mak, T.W., Benchimol, S. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  13. Role of prodomain in importin-mediated nuclear localization and activation of caspase-2. Baliga, B.C., Colussi, P.A., Read, S.H., Dias, M.M., Jans, D.A., Kumar, S. J. Biol. Chem. (2003) [Pubmed]
  14. Requirement for aspartate-cleaved bid in apoptosis signaling by DNA-damaging anti-cancer regimens. Werner, A.B., Tait, S.W., de Vries, E., Eldering, E., Borst, J. J. Biol. Chem. (2004) [Pubmed]
  15. p53-dependent caspase-2 activation in mitochondrial release of apoptosis-inducing factor and its role in renal tubular epithelial cell injury. Seth, R., Yang, C., Kaushal, V., Shah, S.V., Kaushal, G.P. J. Biol. Chem. (2005) [Pubmed]
  16. Bid is upstream of lysosome-mediated caspase 2 activation in tumor necrosis factor alpha-induced hepatocyte apoptosis. Guicciardi, M.E., Bronk, S.F., Werneburg, N.W., Yin, X.M., Gores, G.J. Gastroenterology (2005) [Pubmed]
  17. Mitochondrial release of caspase-2 and -9 during the apoptotic process. Susin, S.A., Lorenzo, H.K., Zamzami, N., Marzo, I., Brenner, C., Larochette, N., Prévost, M.C., Alzari, P.M., Kroemer, G. J. Exp. Med. (1999) [Pubmed]
  18. Sequential caspase-2 and caspase-8 activation upstream of mitochondria during ceramideand etoposide-induced apoptosis. Lin, C.F., Chen, C.L., Chang, W.T., Jan, M.S., Hsu, L.J., Wu, R.H., Tang, M.J., Chang, W.C., Lin, Y.S. J. Biol. Chem. (2004) [Pubmed]
  19. Processing of the Nedd2 precursor by ICE-like proteases and granzyme B. Harvey, N.L., Trapani, J.A., Fernandes-Alnemri, T., Litwack, G., Alnemri, E.S., Kumar, S. Genes Cells (1996) [Pubmed]
  20. Genetic and metabolic status of NGF-deprived sympathetic neurons saved by an inhibitor of ICE family proteases. Deshmukh, M., Vasilakos, J., Deckwerth, T.L., Lampe, P.A., Shivers, B.D., Johnson, E.M. J. Cell Biol. (1996) [Pubmed]
  21. Caspase-2-induced Apoptosis Requires Bid Cleavage: A Physiological Role for Bid in Heat Shock-induced Death. Bonzon, C., Bouchier-Hayes, L., Pagliari, L.J., Green, D.R., Newmeyer, D.D. Mol. Biol. Cell (2006) [Pubmed]
  22. Doxorubicin requires the sequential activation of caspase-2, protein kinase Cdelta, and c-Jun NH2-terminal kinase to induce apoptosis. Panaretakis, T., Laane, E., Pokrovskaja, K., Björklund, A.C., Moustakas, A., Zhivotovsky, B., Heyman, M., Shoshan, M.C., Grandér, D. Mol. Biol. Cell (2005) [Pubmed]
  23. The proteolytic procaspase activation network: an in vitro analysis. Van de Craen, M., Declercq, W., Van den brande, I., Fiers, W., Vandenabeele, P. Cell Death Differ. (1999) [Pubmed]
  24. Caspase-2 is not required for thymocyte or neuronal apoptosis even though cleavage of caspase-2 is dependent on both Apaf-1 and caspase-9. O'Reilly, L.A., Ekert, P., Harvey, N., Marsden, V., Cullen, L., Vaux, D.L., Hacker, G., Magnusson, C., Pakusch, M., Cecconi, F., Kuida, K., Strasser, A., Huang, D.C., Kumar, S. Cell Death Differ. (2002) [Pubmed]
  25. Elevated levels of cysteine protease activity in saliva and salivary glands of the nonobese diabetic (NOD) mouse model for Sjögren syndrome. Robinson, C.P., Yamachika, S., Alford, C.E., Cooper, C., Pichardo, E.L., Shah, N., Peck, A.B., Humphreys-Beher, M.G. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
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