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Gene Review

Casp6  -  caspase 6

Mus musculus

Synonyms: Apoptotic protease Mch-2, CASP-6, Caspase-6, Mch2, mCASP-6
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Disease relevance of Casp6


High impact information on Casp6

  • Furthermore, caspase-6-resistant mutant htt mice are protected against neurotoxicity induced by multiple stressors including NMDA, quinolinic acid (QA), and staurosporine [4].
  • This work provided evidence that CBP is specifically targeted by caspases and calpains at the onset of neuronal apoptosis, and CBP was futher identified as a new caspase-6 substrate [5].
  • K18 is cleaved by caspase-6 into NH2-terminal, 26-kD and COOH-terminal, 22-kD fragments; caspase-3 and -7 additionally cleave the 22-kD fragment into a 19-kD fragment [6].
  • Histologically, at this time there is apoptosis, but no excess deposition of collagen or glycogen. mRNA expression is elevated for caspase 1, caspase 6, and several enzymes associated with sterol biosynthesis and bile acid formation [7].
  • Transcriptional profiling revealed reduced levels of caspase-6 mRNA in p85beta-deficient T cells, which was paralleled by reduced caspase-6 enzyme activity [8].

Biological context of Casp6


Anatomical context of Casp6


Associations of Casp6 with chemical compounds


Enzymatic interactions of Casp6


Regulatory relationships of Casp6

  • In addition, caspase-6 could be activated by the addition of either recombinant caspase-3 or caspase-9 to a lysate prepared from untreated embryos [10].
  • The caspase-6 inhibitor Z-Val-Glu(OMe)-Ile-Asp(OMe)-CH(2)F potently suppressed Akt ubiquitination, degradation, and fragment formation, whereas the proteasome inhibitor Z-Leu-Leu-Leu-CHO modestly attenuated the decline in Akt levels [23].

Other interactions of Casp6


Analytical, diagnostic and therapeutic context of Casp6

  • Transcripts for all three executioner caspases were identified in lens fiber cells by real time RT-PCR, although only caspase-6 and -7 proteins were detected subsequently by Western blot analysis [27].
  • Immunofluorescence microscopy revealed an increased amount of caspase 6, and the active form of caspase 3, in specific regions of the DKO lens, coincident with the site of cell disintegration [28].
  • In the course of apoptosis, caspase-3-like activity increased first at 75 min, simultaneously with the appearance of TUNEL staining and prior to PARP cleavage, and then caspase-6 and 8-like activities increased at 90 and 105 min, respectively [29].


  1. 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]
  2. Early processing of Bid and caspase-6, -8, -10, -14 in the canine brain during cardiac arrest and resuscitation. Krajewska, M., Rosenthal, R.E., Mikolajczyk, J., Stennicke, H.R., Wiesenthal, T., Mai, J., Naito, M., Salvesen, G.S., Reed, J.C., Fiskum, G., Krajewski, S. Exp. Neurol. (2004) [Pubmed]
  3. A caspase-6 and anti-human epidermal growth factor receptor-2 (HER2) antibody chimeric molecule suppresses the growth of HER2-overexpressing tumors. Xu, Y.M., Wang, L.F., Jia, L.T., Qiu, X.C., Zhao, J., Yu, C.J., Zhang, R., Zhu, F., Wang, C.J., Jin, B.Q., Chen, S.Y., Yang, A.G. J. Immunol. (2004) [Pubmed]
  4. Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin. Graham, R.K., Deng, Y., Slow, E.J., Haigh, B., Bissada, N., Lu, G., Pearson, J., Shehadeh, J., Bertram, L., Murphy, Z., Warby, S.C., Doty, C.N., Roy, S., Wellington, C.L., Leavitt, B.R., Raymond, L.A., Nicholson, D.W., Hayden, M.R. Cell (2006) [Pubmed]
  5. Critical loss of CBP/p300 histone acetylase activity by caspase-6 during neurodegeneration. Rouaux, C., Jokic, N., Mbebi, C., Boutillier, S., Loeffler, J.P., Boutillier, A.L. EMBO J. (2003) [Pubmed]
  6. Caspase cleavage of keratin 18 and reorganization of intermediate filaments during epithelial cell apoptosis. Caulín, C., Salvesen, G.S., Oshima, R.G. J. Cell Biol. (1997) [Pubmed]
  7. Cholesterol accumulation and liver cell death in mice with Niemann-Pick type C disease. Beltroy, E.P., Richardson, J.A., Horton, J.D., Turley, S.D., Dietschy, J.M. Hepatology (2005) [Pubmed]
  8. Enhanced T cell proliferation in mice lacking the p85beta subunit of phosphoinositide 3-kinase. Deane, J.A., Trifilo, M.J., Yballe, C.M., Choi, S., Lane, T.E., Fruman, D.A. J. Immunol. (2004) [Pubmed]
  9. Characterization of seven murine caspase family members. Van de Craen, M., Vandenabeele, P., Declercq, W., Van den Brande, I., Van Loo, G., Molemans, F., Schotte, P., Van Criekinge, W., Beyaert, R., Fiers, W. FEBS Lett. (1997) [Pubmed]
  10. Teratogen-induced activation of caspase-6 and caspase-7 in early postimplantation mouse embryos. Little, S.A., Kim, W.K., Mirkes, P.E. Cell Biol. Toxicol. (2003) [Pubmed]
  11. Caspase activity is required for stimulated B lymphocytes to enter the cell cycle. Olson, N.E., Graves, J.D., Shu, G.L., Ryan, E.J., Clark, E.A. J. Immunol. (2003) [Pubmed]
  12. Proteomic analysis of differential protein expression in human nasopharyngeal carcinoma cells induced by NAG7 transfection. Tan, C., Li, J., Wang, J., Xiang, Q., Zhang, X., Dong, L., Shen, S., Liang, S., Li, G. Proteomics (2002) [Pubmed]
  13. Endoplasmic reticulum stress-induced cysteine protease activation in cortical neurons: effect of an Alzheimer's disease-linked presenilin-1 knock-in mutation. Siman, R., Flood, D.G., Thinakaran, G., Neumar, R.W. J. Biol. Chem. (2001) [Pubmed]
  14. Proteolytic mechanisms underlying mitochondrial degradation in the ocular lens. Zandy, A.J., Bassnett, S. Invest. Ophthalmol. Vis. Sci. (2007) [Pubmed]
  15. Staurosporine treatment and serum starvation promote the cleavage of emerin in cultured mouse myoblasts: involvement of a caspase-dependent mechanism. Columbaro, M., Mattioli, E., Lattanzi, G., Rutigliano, C., Ognibene, A., Maraldi, N.M., Squarzoni, S. FEBS Lett. (2001) [Pubmed]
  16. A tripartite anoikis-like mechanism causes early isolated islet apoptosis. Thomas, F., Wu, J., Contreras, J.L., Smyth, C., Bilbao, G., He, J., Thomas, J. Surgery (2001) [Pubmed]
  17. Mechanisms of p75-mediated death of hippocampal neurons. Role of caspases. Troy, C.M., Friedman, J.E., Friedman, W.J. J. Biol. Chem. (2002) [Pubmed]
  18. The in vitro antiapoptotic effect of dehydroepiandrosterone sulfate in mouse thymocytes and its relation to caspase-3/caspase-6. Yan, C.H., Jiang, X.F., Pei, X., Dai, Y.R. Cell. Mol. Life Sci. (1999) [Pubmed]
  19. Sequential activation of caspases and synergistic beta-cell cytotoxicity by palmitate and anti-Fas antibodies. Hirota, N., Otabe, S., Nakayama, H., Yuan, X., Yamada, K. Life Sci. (2006) [Pubmed]
  20. Expression of selected apoptosis related genes, MIF, IGIF and TNF alpha, during retinoic acid-induced neural differentiation in murine embryonic stem cells. Sarkar, S.A., Sharma, R.P. Cell Struct. Funct. (2002) [Pubmed]
  21. Analysis of nuclear apoptotic process in a cell-free system. Zhao, Y., Wu, M., Shen, Y., Zhai, Z. Cell. Mol. Life Sci. (2001) [Pubmed]
  22. The human homologue of the yeast polyubiquitination factor Ufd2p is cleaved by caspase 6 and granzyme B during apoptosis. Mahoney, J.A., Odin, J.A., White, S.M., Shaffer, D., Koff, A., Casciola-Rosen, L., Rosen, A. Biochem. J. (2002) [Pubmed]
  23. Tumor necrosis factor-{alpha} decreases Akt protein levels in 3T3-L1 adipocytes via the caspase-dependent ubiquitination of Akt. Medina, E.A., Afsari, R.R., Ravid, T., Castillo, S.S., Erickson, K.L., Goldkorn, T. Endocrinology (2005) [Pubmed]
  24. 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]
  25. Compensatory caspase activation in MPP+-induced cell death in dopaminergic neurons. Chee, J.L., Guan, X.L., Lee, J.Y., Dong, B., Leong, S.M., Ong, E.H., Liou, A.K., Lim, T.M. Cell. Mol. Life Sci. (2005) [Pubmed]
  26. Therapeutic efficacy of PUMA for malignant glioma cells regardless of p53 status. Ito, H., Kanzawa, T., Miyoshi, T., Hirohata, S., Kyo, S., Iwamaru, A., Aoki, H., Kondo, Y., Kondo, S. Hum. Gene Ther. (2005) [Pubmed]
  27. Role of the executioner caspases during lens development. Zandy, A.J., Lakhani, S., Zheng, T., Flavell, R.A., Bassnett, S. J. Biol. Chem. (2005) [Pubmed]
  28. Caspase-dependent secondary lens fiber cell disintegration in alphaA-/alphaB-crystallin double-knockout mice. Morozov, V., Wawrousek, E.F. Development (2006) [Pubmed]
  29. Changes of caspase activities involved in apoptosis of a macrophage-like cell line J774.1/JA-4 treated with lipopolysaccharide (LPS) and cycloheximide. Karahashi, H., Amano, F. Biol. Pharm. Bull. (2000) [Pubmed]
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