Caspase 6

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RefSeq (mRNA)



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Caspase-6 is an enzyme that in humans is encoded by the CASP6 gene.[1][2] CASP6 orthologs [3] have been identified in numerous mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts. Caspase-6 has known functions in apoptosis[4], early immune response[5][6] and neurodegeneration in Huntington's and Alzheimer's disease.[7]


This gene encodes a protein that is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis.[4] Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein is processed by caspases 7, 8 and 10, and is thought to function as a downstream enzyme in the caspase activation cascade. Caspase 6 can also undergo self-processing without other members of the caspase family.[8] Alternative splicing of this gene results in two transcript variants that encode different isoforms.[9]

Caspase-6 plays a role in the early immune response via de-repression. It reduces the expression of the immunosuppressant cytokine interleukin-10[5] and cleaves the macrophage suppressing IRAK-M.[6]

With respect to neurodegeneration, caspase-6 cleaves HTT in Huntington's and APP in Alzheimer's disease. Resulting in both cases in protein aggregation of the fragments.[7]


Caspase 6 has been shown to interact with Caspase 8.[10][11][12]

See also


  1. Tiso N, Pallavicini A, Muraro T, Zimbello R, Apolloni E, Valle G, Lanfranchi G, Danieli GA (Oct 1996). "Chromosomal localization of the human genes, CPP32, Mch2, Mch3, and Ich-1, involved in cellular apoptosis". Biochem Biophys Res Commun. 225 (3): 983–9. doi:10.1006/bbrc.1996.1282. PMID 8780721.
  2. Fernandes-Alnemri T, Litwack G, Alnemri ES (Aug 1995). "Mch2, a new member of the apoptotic Ced-3/Ice cysteine protease gene family". Cancer Res. 55 (13): 2737–42. PMID 7796396.
  3. "OrthoMaM phylogenetic marker: CASP6 coding sequence".
  4. 4.0 4.1 Cohen, Gerald M. (1997-08-15). "Caspases: the executioners of apoptosis". Biochemical Journal. 326 (1): 1–16. doi:10.1042/bj3260001. ISSN 0264-6021. PMC 1218630. PMID 9337844.
  5. 5.0 5.1 Bartel, Alexander; Göhler, André; Hopf, Verena; Breitbach, Katrin (2017-07-07). "Caspase-6 mediates resistance against Burkholderia pseudomallei infection and influences the expression of detrimental cytokines". PLOS ONE. 12 (7): e0180203. doi:10.1371/journal.pone.0180203. ISSN 1932-6203.
  6. 6.0 6.1 Kobayashi, Hiroshi; Nolan, Anna; Naveed, Bushra; Hoshino, Yoshihiko; Segal, Leopoldo N.; Fujita, Yoko; Rom, William N.; Weiden, Michael D. (2011-01-01). "Neutrophils Activate Alveolar Macrophages by Producing Caspase-6–Mediated Cleavage of IL-1 Receptor-Associated Kinase-M". The Journal of Immunology. 186 (1): 403–410. doi:10.4049/jimmunol.1001906. ISSN 0022-1767. PMC 3151149. PMID 21098228.
  7. 7.0 7.1 Graham, Rona K.; Ehrnhoefer, Dagmar E.; Hayden, Michael R. (2011-12-01). "Caspase-6 and neurodegeneration". Trends in Neurosciences. 34 (12): 646–656. doi:10.1016/j.tins.2011.09.001. ISSN 0166-2236. PMID 22018804.
  8. Wang XJ, Cao Q, Liu X, Wang KT, Mi W, Zhang Y, Li LF, LeBlanc AC, Su XD (Nov 2010). "Crystal structures of human caspase 6 reveal a new mechanism for intramolecular cleavage self-activation". EMBO Rep. 11 (11): 841–7. doi:10.1038/embor.2010.141. PMC 2966951. PMID 20890311.
  9. "Entrez Gene: CASP6 caspase 6, apoptosis-related cysteine peptidase".
  10. Cowling V, Downward J (Oct 2002). "Caspase-6 is the direct activator of caspase-8 in the cytochrome c-induced apoptosis pathway: absolute requirement for removal of caspase-6 prodomain". Cell Death Differ. 9 (10): 1046–56. doi:10.1038/sj.cdd.4401065. PMID 12232792.
  11. Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T, Alnemri ES (Apr 2002). "Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria". J. Biol. Chem. 277 (16): 13430–7. doi:10.1074/jbc.M108029200. PMID 11832478.
  12. Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri ES (Dec 1996). "Molecular ordering of the Fas-apoptotic pathway: The Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases". Proc. Natl. Acad. Sci. U.S.A. 93 (25): 14486–91. doi:10.1073/pnas.93.25.14486. PMC 26159. PMID 8962078.

Further reading

External links

  • The MEROPS online database for peptidases and their inhibitors: C14.005