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Gene Review

Casp1  -  caspase 1

Mus musculus

Synonyms: CASP-1, Caspase-1, ICE, IL-1 beta-converting enzyme, IL-1BC, ...
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Disease relevance of Casp1


Psychiatry related information on Casp1


High impact information on Casp1

  • Recent evidence has indicated that the caspase family of cysteine proteases is a central effector in apoptotic cell death and is absolutely responsible for many of the morphological features of apoptosis [7].
  • In contrast, healthy cells require caspase activation to undergo cell death induced by surface receptors [7].
  • We also show that LeTx-induced macrophage death requires caspase-1, which is activated in susceptible, but not resistant, macrophages after intoxication, suggesting that Nalp1b directly or indirectly activates caspase-1 in response to LeTx [8].
  • These studies indicate the existence of a Cyt c- and apoptosome-independent but Apaf-1-dependent mechanism(s) for caspase activation [9].
  • As components of the apoptosome, a caspase-activating complex, cytochrome c (Cyt c) and Apaf-1 are thought to play critical roles during apoptosis [9].

Chemical compound and disease context of Casp1


Biological context of Casp1


Anatomical context of Casp1

  • Caspase-cleaved gelsolin severed actin filaments in vitro in a Ca2+-independent manner [19].
  • Salmonella exploits caspase-1 to colonize Peyer's patches in a murine typhoid model [10].
  • Furthermore, Salmonella did not disseminate systemically in the majority of casp-1(-/)- mice, as demonstrated by significantly less colonization in the PP, mesenteric lymph nodes, and spleens of casp-1(-/)- mice after an oral dose of S. typhimurium that was 100-fold higher than the LD(50) [10].
  • These results show that Casp-1, which is both proapoptotic and proinflammatory, is essential for S. typhimurium to efficiently colonize the cecum and PP and subsequently cause systemic typhoid-like disease in mice [10].
  • Finally, we confirmed histologically that caspase-1(-/-) mice show decreased neutrophil infiltration, indicating that the deleterious role of IL-18 in ischemic ARF may be due to increased neutrophil infiltration [17].

Associations of Casp1 with chemical compounds


Physical interactions of Casp1

  • Focal in vivo inhibition of initiator caspase activation or microtubule-dependent transport (with Taxol) at the lesioned axon terminus results in a significant reduction in retrograde axonal caspase-8 and caspase-3 activation and inhibition of retrograde ORN death [25].
  • Caspase recruitment domain protein 6 is a microtubule-interacting protein that positively modulates NF-kappaB activation [26].

Enzymatic interactions of Casp1


Regulatory relationships of Casp1


Other interactions of Casp1

  • The cellular production of IL-1beta, a cytokine implicated in a variety of inflammatory diseases, requires cleavage of its precursor (proIL-1beta) at an Asp-X site by interleukin-1beta-converting enzyme (ICE, recently termed caspase-1) [36].
  • Here, we demonstrate the effect of NALP3 deficiency on caspase-1 function [2].
  • We conclude that Bcl-2 has cytoprotective functions independent of Apaf-1, preserving mitochondrial function through a caspase-independent mechanism [31].
  • In contrast, STS, UVB, and VP16 induced little or no caspase activation and apoptosis in homozygous (-/-) Apaf-1 knockout ES cells [31].
  • Impaired IL-18 processing protects caspase-1-deficient mice from ischemic acute renal failure [17].

Analytical, diagnostic and therapeutic context of Casp1


  1. 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]
  2. Critical role for NALP3/CIAS1/Cryopyrin in innate and adaptive immunity through its regulation of caspase-1. Sutterwala, F.S., Ogura, Y., Szczepanik, M., Lara-Tejero, M., Lichtenberger, G.S., Grant, E.P., Bertin, J., Coyle, A.J., Galán, J.E., Askenase, P.W., Flavell, R.A. Immunity (2006) [Pubmed]
  3. Caspase-1 activation of IL-1beta and IL-18 are essential for Shigella flexneri-induced inflammation. Sansonetti, P.J., Phalipon, A., Arondel, J., Thirumalai, K., Banerjee, S., Akira, S., Takeda, K., Zychlinsky, A. Immunity (2000) [Pubmed]
  4. Caspase inhibitors improve survival in sepsis: a critical role of the lymphocyte. Hotchkiss, R.S., Chang, K.C., Swanson, P.E., Tinsley, K.W., Hui, J.J., Klender, P., Xanthoudakis, S., Roy, S., Black, C., Grimm, E., Aspiotis, R., Han, Y., Nicholson, D.W., Karl, I.E. Nat. Immunol. (2000) [Pubmed]
  5. Specific caspase interactions and amplification are involved in selective neuronal vulnerability in Huntington's disease. Hermel, E., Gafni, J., Propp, S.S., Leavitt, B.R., Wellington, C.L., Young, J.E., Hackam, A.S., Logvinova, A.V., Peel, A.L., Chen, S.F., Hook, V., Singaraja, R., Krajewski, S., Goldsmith, P.C., Ellerby, H.M., Hayden, M.R., Bredesen, D.E., Ellerby, L.M. Cell Death Differ. (2004) [Pubmed]
  6. Amyloid beta protein toxicity mediated by the formation of amyloid-beta protein precursor complexes. Lu, D.C., Shaked, G.M., Masliah, E., Bredesen, D.E., Koo, E.H. Ann. Neurol. (2003) [Pubmed]
  7. The central effectors of cell death in the immune system. Rathmell, J.C., Thompson, C.B. Annu. Rev. Immunol. (1999) [Pubmed]
  8. Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin. Boyden, E.D., Dietrich, W.F. Nat. Genet. (2006) [Pubmed]
  9. Specific ablation of the apoptotic functions of cytochrome C reveals a differential requirement for cytochrome C and Apaf-1 in apoptosis. Hao, Z., Duncan, G.S., Chang, C.C., Elia, A., Fang, M., Wakeham, A., Okada, H., Calzascia, T., Jang, Y., You-Ten, A., Yeh, W.C., Ohashi, P., Wang, X., Mak, T.W. Cell (2005) [Pubmed]
  10. Salmonella exploits caspase-1 to colonize Peyer's patches in a murine typhoid model. Monack, D.M., Hersh, D., Ghori, N., Bouley, D., Zychlinsky, A., Falkow, S. J. Exp. Med. (2000) [Pubmed]
  11. 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]
  12. Role of caspase 1 in murine antibacterial host defenses and lethal endotoxemia. Joshi, V.D., Kalvakolanu, D.V., Hebel, J.R., Hasday, J.D., Cross, A.S. Infect. Immun. (2002) [Pubmed]
  13. Genetic Susceptibility and Caspase Activation in Mouse and Human Macrophages Are Distinct for Legionella longbeachae and L. pneumophila. Asare, R., Santic, M., Gobin, I., Doric, M., Suttles, J., Graham, J.E., Price, C.D., Abu Kwaik, Y. Infect. Immun. (2007) [Pubmed]
  14. Caspase-dependent apoptosis induction by guggulsterone, a constituent of Ayurvedic medicinal plant Commiphora mukul, in PC-3 human prostate cancer cells is mediated by Bax and Bak. Singh, S.V., Zeng, Y., Xiao, D., Vogel, V.G., Nelson, J.B., Dhir, R., Tripathi, Y.B. Mol. Cancer Ther. (2005) [Pubmed]
  15. Caspase 1-independent IL-1beta release and inflammation induced by the apoptosis inducer Fas ligand. Miwa, K., Asano, M., Horai, R., Iwakura, Y., Nagata, S., Suda, T. Nat. Med. (1998) [Pubmed]
  16. A stress-induced, superoxide-mediated caspase-1 activation pathway causes plasma IL-18 upregulation. Sekiyama, A., Ueda, H., Kashiwamura, S., Sekiyama, R., Takeda, M., Rokutan, K., Okamura, H. Immunity (2005) [Pubmed]
  17. Impaired IL-18 processing protects caspase-1-deficient mice from ischemic acute renal failure. Melnikov, V.Y., Ecder, T., Fantuzzi, G., Siegmund, B., Lucia, M.S., Dinarello, C.A., Schrier, R.W., Edelstein, C.L. J. Clin. Invest. (2001) [Pubmed]
  18. Fundamental role of the Rip2/caspase-1 pathway in hypoxia and ischemia-induced neuronal cell death. Zhang, W.H., Wang, X., Narayanan, M., Zhang, Y., Huo, C., Reed, J.C., Friedlander, R.M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  19. 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]
  20. An NO derivative of ursodeoxycholic acid protects against Fas-mediated liver injury by inhibiting caspase activity. Fiorucci, S., Mencarelli, A., Palazzetti, B., Del Soldato, P., Morelli, A., Ignarro, L.J. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  21. Interferon-gamma-induced apoptotic responses of Fanconi anemia group C hematopoietic progenitor cells involve caspase 8-dependent activation of caspase 3 family members. Rathbun, R.K., Christianson, T.A., Faulkner, G.R., Jones, G., Keeble, W., O'Dwyer, M., Bagby, G.C. Blood (2000) [Pubmed]
  22. 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]
  23. Critical role for cathepsin B in mediating caspase-1-dependent interleukin-18 maturation and caspase-1-independent necrosis triggered by the microbial toxin nigericin. Hentze, H., Lin, X.Y., Choi, M.S., Porter, A.G. Cell Death Differ. (2003) [Pubmed]
  24. Proteasomes control caspase-1 activation in anthrax lethal toxin-mediated cell killing. Squires, R.C., Muehlbauer, S.M., Brojatsch, J. J. Biol. Chem. (2007) [Pubmed]
  25. Axonal dynactin p150Glued transports caspase-8 to drive retrograde olfactory receptor neuron apoptosis. Carson, C., Saleh, M., Fung, F.W., Nicholson, D.W., Roskams, A.J. J. Neurosci. (2005) [Pubmed]
  26. Caspase recruitment domain protein 6 is a microtubule-interacting protein that positively modulates NF-kappaB activation. Dufner, A., Pownall, S., Mak, T.W. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  27. Caspase cleavage of mutant huntingtin precedes neurodegeneration in Huntington's disease. Wellington, C.L., Ellerby, L.M., Gutekunst, C.A., Rogers, D., Warby, S., Graham, R.K., Loubser, O., van Raamsdonk, J., Singaraja, R., Yang, Y.Z., Gafni, J., Bredesen, D., Hersch, S.M., Leavitt, B.R., Roy, S., Nicholson, D.W., Hayden, M.R. J. Neurosci. (2002) [Pubmed]
  28. Potentiation of caspase-1 activation by the P2X7 receptor is dependent on TLR signals and requires NF-kappaB-driven protein synthesis. Kahlenberg, J.M., Lundberg, K.C., Kertesy, S.B., Qu, Y., Dubyak, G.R. J. Immunol. (2005) [Pubmed]
  29. Poly(ADP-ribose)polymerase activation mediates lung epithelial cell death in vitro but is not essential in hyperoxia-induced lung injury. Pagano, A., Pitteloud, C., Reverdin, C., Métrailler-Ruchonnet, I., Donati, Y., Barazzone Argiroffo, C. Am. J. Respir. Cell Mol. Biol. (2005) [Pubmed]
  30. In vivo and in vitro sensitization of leukemic cells to adriamycin-induced apoptosis by pentoxifylline. Involvement of caspase cascades and IkappaBalpha phosphorylation. Lerma-Díaz, J.M., Hernández-Flores, G., Domínguez-Rodríguez, J.R., Ortíz-Lazareno, P.C., Gómez-Contreras, P., Cervantes-Munguía, R., Scott-Algara, D., Aguilar-Lemarroy, A., Jave-Suárez, L.F., Bravo-Cuellar, A. Immunol. Lett. (2006) [Pubmed]
  31. Apoptotic protease activating factor 1 (Apaf-1)-independent cell death suppression by Bcl-2. Haraguchi, M., Torii, S., Matsuzawa, S., Xie, Z., Kitada, S., Krajewski, S., Yoshida, H., Mak, T.W., Reed, J.C. J. Exp. Med. (2000) [Pubmed]
  32. Nitric oxide prevents IL-1beta and IFN-gamma-inducing factor (IL-18) release from macrophages by inhibiting caspase-1 (IL-1beta-converting enzyme). Kim, Y.M., Talanian, R.V., Li, J., Billiar, T.R. J. Immunol. (1998) [Pubmed]
  33. Regulation of the expression of caspase-9 by the transcription factor activator protein-4 in glucocorticoid-induced apoptosis. Tsujimoto, K., Ono, T., Sato, M., Nishida, T., Oguma, T., Tadakuma, T. J. Biol. Chem. (2005) [Pubmed]
  34. Expression analysis of the human caspase-1 subfamily reveals specific regulation of the CASP5 gene by lipopolysaccharide and interferon-gamma. Lin, X.Y., Choi, M.S., Porter, A.G. J. Biol. Chem. (2000) [Pubmed]
  35. Differential requirement of P2X7 receptor and intracellular K+ for caspase-1 activation induced by intracellular and extracellular bacteria. Franchi, L., Kanneganti, T.D., Dubyak, G.R., Núñez, G. J. Biol. Chem. (2007) [Pubmed]
  36. Caspase-1 processes IFN-gamma-inducing factor and regulates LPS-induced IFN-gamma production. Ghayur, T., Banerjee, S., Hugunin, M., Butler, D., Herzog, L., Carter, A., Quintal, L., Sekut, L., Talanian, R., Paskind, M., Wong, W., Kamen, R., Tracey, D., Allen, H. Nature (1997) [Pubmed]
  37. Progressive resistance to apoptosis in a cell lineage model of human proliferative breast disease. Starcevic, S.L., Elferink, C., Novak, R.F. J. Natl. Cancer Inst. (2001) [Pubmed]
  38. Gene expression, synthesis, and secretion of interleukin 18 and interleukin 1beta are differentially regulated in human blood mononuclear cells and mouse spleen cells. Puren, A.J., Fantuzzi, G., Dinarello, C.A. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  39. 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]
  40. Caspase-1-processed interleukins in hyperoxia-induced cell death in the developing brain. Felderhoff-Mueser, U., Sifringer, M., Polley, O., Dzietko, M., Leineweber, B., Mahler, L., Baier, M., Bittigau, P., Obladen, M., Ikonomidou, C., Bührer, C. Ann. Neurol. (2005) [Pubmed]
  41. Interleukin-1beta and signaling of interleukin-1 in vascular wall and circulating cells modulates the extent of neointima formation in mice. Chamberlain, J., Evans, D., King, A., Dewberry, R., Dower, S., Crossman, D., Francis, S. Am. J. Pathol. (2006) [Pubmed]
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