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Gene Review

CASP3  -  caspase 3, apoptosis-related cysteine...

Homo sapiens

Synonyms: Apopain, CASP-3, CPP-32, CPP32, CPP32B, ...
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Disease relevance of CASP3


Psychiatry related information on CASP3


High impact information on CASP3

  • Our findings suggest that Apaf1 is essential for Casp3 activation in embryonic brain and is a key regulator of developmental programmed cell death in mammals [10].
  • Here we show that apoptotic extracts and apopain itself specifically cleave the HD gene product, huntingtin [11].
  • Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract [11].
  • We also examined the level of expression of CPP-32, a cysteine protease required for apoptotic cell death in mammalian cells, using immunohistochemical techniques [12].
  • Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase [13].

Chemical compound and disease context of CASP3


Biological context of CASP3


Anatomical context of CASP3


Associations of CASP3 with chemical compounds

  • Additionally, NS-398 treatment increased expression of apoptotic genes such as BAD, STAT1, and CASP3 [26].
  • Apopain, a human counterpart of the nematode cysteine protease death-gene product, CED-3, has a key role in proteolytic events leading to apoptosis [11].
  • A potent peptide aldehyde inhibitor has been developed and shown to prevent apoptotic events in vitro, suggesting that apopain/CPP32 is important for the initiation of apoptotic cell death [27].
  • Like PARP, cleavage of these substrates in apoptotic cell extracts is abolished by nanomolar concentrations of Ac-DEVD-CHO and micromolar amounts of Ac-YVAD-CHO, confirming the involvement of apopain or an apopain-like activity [28].
  • Whether SCA/CPP32 participates in vivo in the sterol-regulated activation of SREBP, or whether it activates SREBPs during apoptosis, remains to be determined [25].

Enzymatic interactions of CASP3

  • Furthermore, DNA-PKcs was cleaved in vitro by purified apopain (CPP32), but not IL-1beta-converting enzyme [29].
  • We report herein that p21 was cleaved by caspase-3/CPP32 at the site of DHVD112L during the DNA damage-induced apoptosis of cancer cells [30].
  • We demonstrate that the pro-enzymes of Mch6 and the lamin-cleaving enzyme Mch2alpha are substrates for mature CPP32 [31].
  • MDM2 is cleaved by Caspase 3 (CPP32) during apoptosis after aspartic acid-361, generating a 60 kd fragment [32].
  • In vitro, CPP32 cleaves recombinant gamma-PAK into two peptides; 1-212 contains the majority of the regulatory domain whereas 213-524 contains 34 amino acids of the regulatory domain plus the entire catalytic domain [33].

Regulatory relationships of CASP3


Other interactions of CASP3


Analytical, diagnostic and therapeutic context of CASP3


  1. Neuronal death in brain infarcts in man. Love, S., Barber, R., Wilcock, G.K. Neuropathol. Appl. Neurobiol. (2000) [Pubmed]
  2. Mutational analysis of the CASP6 gene in colorectal and gastric carcinomas. Lee, J.W., Kim, M.R., Soung, Y.H., Nam, S.W., Kim, S.H., Lee, J.Y., Yoo, N.J., Lee, S.H. APMIS (2006) [Pubmed]
  3. Activation of apoptosis by Apo-2 ligand is independent of FADD but blocked by CrmA. Marsters, S.A., Pitti, R.M., Donahue, C.J., Ruppert, S., Bauer, K.D., Ashkenazi, A. Curr. Biol. (1996) [Pubmed]
  4. Sendai virus infection induces apoptosis through activation of caspase-8 (FLICE) and caspase-3 (CPP32). Bitzer, M., Prinz, F., Bauer, M., Spiegel, M., Neubert, W.J., Gregor, M., Schulze-Osthoff, K., Lauer, U. J. Virol. (1999) [Pubmed]
  5. Cysteine protease CPP32, but not Ich1-L, is expressed in germinal center B cells and their neoplastic counterparts. Xerri, L., Devilard, E., Ayello, C., Brousset, P., Reed, J.C., Emile, J.F., Hassoun, J., Parmentier, S., Birg, F. Hum. Pathol. (1997) [Pubmed]
  6. Caspase-3 activity predicts local recurrence in rectal cancer. de Heer, P., de Bruin, E.C., Klein-Kranenbarg, E., Aalbers, R.I., Marijnen, C.A., Putter, H., de Bont, H.J., Nagelkerke, J.F., van Krieken, J.H., Verspaget, H.W., van de Velde, C.J., Kuppen, P.J. Clin. Cancer Res. (2007) [Pubmed]
  7. Prognostic significance of the immunohistochemical staining of cleaved caspase-3, an activated form of caspase-3, in gliomas. Kobayashi, T., Masumoto, J., Tada, T., Nomiyama, T., Hongo, K., Nakayama, J. Clin. Cancer Res. (2007) [Pubmed]
  8. Alteration of proteins regulating apoptosis, Bcl-2, Bcl-x, Bax, Bak, Bad, ICH-1 and CPP32, in Alzheimer's disease. Kitamura, Y., Shimohama, S., Kamoshima, W., Ota, T., Matsuoka, Y., Nomura, Y., Smith, M.A., Perry, G., Whitehouse, P.J., Taniguchi, T. Brain Res. (1998) [Pubmed]
  9. Clinical and molecular findings in the first identified Italian family with dentatorubral-pallidoluysian atrophy. Villani, F., Gellera, C., Spreafico, R., Castellotti, B., Casazza, M., Carrara, F., Avanzini, G. Acta neurologica Scandinavica. (1998) [Pubmed]
  10. Apaf1 (CED-4 homolog) regulates programmed cell death in mammalian development. Cecconi, F., Alvarez-Bolado, G., Meyer, B.I., Roth, K.A., Gruss, P. Cell (1998) [Pubmed]
  11. Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract. Goldberg, Y.P., Nicholson, D.W., Rasper, D.M., Kalchman, M.A., Koide, H.B., Graham, R.K., Bromm, M., Kazemi-Esfarjani, P., Thornberry, N.A., Vaillancourt, J.P., Hayden, M.R. Nat. Genet. (1996) [Pubmed]
  12. Evidence of apoptosis in arrhythmogenic right ventricular dysplasia. Mallat, Z., Tedgui, A., Fontaliran, F., Frank, R., Durigon, M., Fontaine, G. N. Engl. J. Med. (1996) [Pubmed]
  13. Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase. Tewari, M., Quan, L.T., O'Rourke, K., Desnoyers, S., Zeng, Z., Beidler, D.R., Poirier, G.G., Salvesen, G.S., Dixit, V.M. Cell (1995) [Pubmed]
  14. Overexpression of Bcl-2 or Bcl-xL inhibits Ara-C-induced CPP32/Yama protease activity and apoptosis of human acute myelogenous leukemia HL-60 cells. Ibrado, A.M., Huang, Y., Fang, G., Liu, L., Bhalla, K. Cancer Res. (1996) [Pubmed]
  15. Induction of programmed cell death by parvovirus H-1 in U937 cells: connection with the tumor necrosis factor alpha signalling pathway. Rayet, B., Lopez-Guerrero, J.A., Rommelaere, J., Dinsart, C. J. Virol. (1998) [Pubmed]
  16. Release of mitochondrial cytochrome C in both apoptosis and necrosis induced by beta-lapachone in human carcinoma cells. Li, Y.Z., Li, C.J., Pinto, A.V., Pardee, A.B. Mol. Med. (1999) [Pubmed]
  17. TNF-alpha induces apoptosis mediated by AEBSF-sensitive serine protease(s) that may involve upstream caspase-3/CPP32 protease activation in a human gastric cancer cell line. Park, I.C., Park, M.J., Choe, T.B., Jang, J.J., Hong, S.I., Lee, S.H. Int. J. Oncol. (2000) [Pubmed]
  18. Cell death in polyglutamine diseases. Evert, B.O., Wüllner, U., Klockgether, T. Cell Tissue Res. (2000) [Pubmed]
  19. A primate-specific acceleration in the evolution of the caspase-dependent apoptosis pathway. Vallender, E.J., Lahn, B.T. Hum. Mol. Genet. (2006) [Pubmed]
  20. Nonoxynol-9 induces apoptosis of endometrial explants by both caspase-dependent and -independent apoptotic pathways. Jain, J.K., Li, A., Nucatola, D.L., Minoo, P., Felix, J.C. Biol. Reprod. (2005) [Pubmed]
  21. Cloning of the bovine antiapoptotic regulator, BCL2-related protein A1, and its expression in trophoblastic binucleate cells of bovine placenta. Ushizawa, K., Takahashi, T., Kaneyama, K., Hosoe, M., Hashizume, K. Biol. Reprod. (2006) [Pubmed]
  22. p21(WAF1/CIP1) inhibits initiator caspase cleavage by TRAIL death receptor DR4. Xu, S.Q., El-Deiry, W.S. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  23. The central executioner of apoptosis: multiple connections between protease activation and mitochondria in Fas/APO-1/CD95- and ceramide-induced apoptosis. Susin, S.A., Zamzami, N., Castedo, M., Daugas, E., Wang, H.G., Geley, S., Fassy, F., Reed, J.C., Kroemer, G. J. Exp. Med. (1997) [Pubmed]
  24. CPP32/apopain is a key interleukin 1 beta converting enzyme-like protease involved in Fas-mediated apoptosis. Schlegel, J., Peters, I., Orrenius, S., Miller, D.K., Thornberry, N.A., Yamin, T.T., Nicholson, D.W. J. Biol. Chem. (1996) [Pubmed]
  25. Purification of an interleukin-1 beta converting enzyme-related cysteine protease that cleaves sterol regulatory element-binding proteins between the leucine zipper and transmembrane domains. Wang, X., Pai, J.T., Wiedenfeld, E.A., Medina, J.C., Slaughter, C.A., Goldstein, J.L., Brown, M.S. J. Biol. Chem. (1995) [Pubmed]
  26. NSAIDs activate PTEN and other phosphatases in human colon cancer cells: novel mechanism for chemopreventive action of NSAIDs. Chu, E.C., Chai, J., Tarnawski, A.S. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  27. Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nicholson, D.W., Ali, A., Thornberry, N.A., Vaillancourt, J.P., Ding, C.K., Gallant, M., Gareau, Y., Griffin, P.R., Labelle, M., Lazebnik, Y.A. Nature (1995) [Pubmed]
  28. Apopain/CPP32 cleaves proteins that are essential for cellular repair: a fundamental principle of apoptotic death. Casciola-Rosen, L., Nicholson, D.W., Chong, T., Rowan, K.R., Thornberry, N.A., Miller, D.K., Rosen, A. J. Exp. Med. (1996) [Pubmed]
  29. The DNA-dependent protein kinase catalytic subunit (p460) is cleaved during Fas-mediated apoptosis in Jurkat cells. McConnell, K.R., Dynan, W.S., Hardin, J.A. J. Immunol. (1997) [Pubmed]
  30. Caspase-mediated cleavage of p21Waf1/Cip1 converts cancer cells from growth arrest to undergoing apoptosis. Zhang, Y., Fujita, N., Tsuruo, T. Oncogene (1999) [Pubmed]
  31. The Ced-3/interleukin 1beta converting enzyme-like homolog Mch6 and the lamin-cleaving enzyme Mch2alpha are substrates for the apoptotic mediator CPP32. Srinivasula, S.M., Fernandes-Alnemri, T., Zangrilli, J., Robertson, N., Armstrong, R.C., Wang, L., Trapani, J.A., Tomaselli, K.J., Litwack, G., Alnemri, E.S. J. Biol. Chem. (1996) [Pubmed]
  32. A 60 kd MDM2 isoform is produced by caspase cleavage in non-apoptotic tumor cells. Pochampally, R., Fodera, B., Chen, L., Shao, W., Levine, E.A., Chen, J. Oncogene (1998) [Pubmed]
  33. Cleavage and activation of p21-activated protein kinase gamma-PAK by CPP32 (caspase 3). Effects of autophosphorylation on activity. Walter, B.N., Huang, Z., Jakobi, R., Tuazon, P.T., Alnemri, E.S., Litwack, G., Traugh, J.A. J. Biol. Chem. (1998) [Pubmed]
  34. Oligonucleosomal DNA fragmentation in MCF-7 cells undergoing palmitate-induced apoptosis. Semenov, D.V., Aronov, P.A., Kuligina, E.V., Potapenko, M.O., Richter, V.A. Biochemistry Mosc. (2003) [Pubmed]
  35. Proteolytic cleavage and activation of PAK2 during UV irradiation-induced apoptosis in A431 cells. Tang, T.K., Chang, W.C., Chan, W.H., Yang, S.D., Ni, M.H., Yu, J.S. J. Cell. Biochem. (1998) [Pubmed]
  36. Transforming growth factor beta 1 potently activates CPP32-like proteases in human hepatoma cells. Hung, W.C., Chang, H.C., Chuang, L.Y. Cell. Signal. (1998) [Pubmed]
  37. IRF-1-mediated CAS expression enhances interferon-gamma-induced apoptosis of HT-29 colon adenocarcinoma cells. Jiang, M.C., Lin, T.L., Lee, T.L., Huang, H.T., Lin, C.L., Liao, C.F. Mol. Cell Biol. Res. Commun. (2001) [Pubmed]
  38. Binding of caspase-3 prodomain to heat shock protein 27 regulates monocyte apoptosis by inhibiting caspase-3 proteolytic activation. Voss, O.H., Batra, S., Kolattukudy, S.J., Gonzalez-Mejia, M.E., Smith, J.B., Doseff, A.I. J. Biol. Chem. (2007) [Pubmed]
  39. In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains. Fernandes-Alnemri, T., Armstrong, R.C., Krebs, J., Srinivasula, S.M., Wang, L., Bullrich, F., Fritz, L.C., Trapani, J.A., Tomaselli, K.J., Litwack, G., Alnemri, E.S. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  40. Interferon gamma induces upregulation and activation of caspases 1, 3, and 8 to produce apoptosis in human erythroid progenitor cells. Dai, C., Krantz, S.B. Blood (1999) [Pubmed]
  41. Identification and characterization of CPP32/Mch2 homolog 1, a novel cysteine protease similar to CPP32. Lippke, J.A., Gu, Y., Sarnecki, C., Caron, P.R., Su, M.S. J. Biol. Chem. (1996) [Pubmed]
  42. Upregulation of CASP genes in human tumor cells undergoing etoposide-induced apoptosis. Droin, N., Dubrez, L., Eymin, B., Renvoizé, C., Bréard, J., Dimanche-Boitrel, M.T., Solary, E. Oncogene (1998) [Pubmed]
  43. Epigallocatechin gallate reduces hypoxia-induced apoptosis in human hepatoma cells. Park, H.J., Shin, D.H., Chung, W.J., Leem, K., Yoon, S.H., Hong, M.S., Chung, J.H., Bae, J.H., Hwang, J.S. Life Sci. (2006) [Pubmed]
  44. Activation of caspases in p53-induced transactivation-independent apoptosis. Gao, C., Tsuchida, N. Jpn. J. Cancer Res. (1999) [Pubmed]
  45. Ligation of CD40 potentiates Fas-mediated activation of the cysteine protease CPP32, cleavage of its death substrate PARP, and apoptosis in Ramos-Burkitt lymphoma B cells. An, S., Yap, D., Knox, K.A. Cell. Immunol. (1997) [Pubmed]
  46. Interleukin-1 beta-converting enzyme-like protease cleaves DNA-dependent protein kinase in cytotoxic T cell killing. Song, Q., Burrows, S.R., Smith, G., Lees-Miller, S.P., Kumar, S., Chan, D.W., Trapani, J.A., Alnemri, E., Litwack, G., Lu, H., Moss, D.J., Jackson, S., Lavin, M.F. J. Exp. Med. (1996) [Pubmed]
  47. Fas-L up-regulation by highly malignant myeloma plasma cells: role in the pathogenesis of anemia and disease progression. Silvestris, F., Tucci, M., Cafforio, P., Dammacco, F. Blood (2001) [Pubmed]
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