EC 3.4.22.59 - Caspase-6

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IntEnz Enzyme Nomenclature
EC 3.4.22.59

Names

Accepted name:
caspase-6
Other names:
CASP-6
apoptotic protease Mch-2
Mch2
Systematic name:
-

Reaction

Comments:

Caspase-6 is an effector/executioner caspase, as are caspase-3 (EC 3.4.22.56) and caspase-7 (EC 3.4.22.60) [2]. These caspases are responsible for the proteolysis of the majority of cellular polypeptides, [e.g. poly(ADP-ribose) polymerase (PARP)], which lead to the apoptotic phenotype [2]. Caspase-6 can cleave its prodomain to produce mature caspase-6, which directly activates caspase-8 (EC 3.4.22.61) and leads to cytochrome c release from the mitochondria. The release of cytochrome c is an essential component of the intrinsic apoptosis pathway [1]. The enzyme can also cleave and inactivate lamins, the intermediate filament scaffold proteins of the nuclear envelope, leading to nuclear fragementation in the final phases of apoptosis [2,4,5,6]. Belongs in peptidase family C14.

Links to other databases

Enzymes and pathways: NC-IUBMB , BRENDA , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , MEROPS , UniPathway
Protein domains and families: PROSITE:PDOC00864
Structural data: CSA , EC2PDB
UniProtKB/Swiss-Prot:

References

  1. Cowling, V. and Downward, J.
    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: 1046-1056 (2002). [PMID: 12232792]
  2. Chang, H.Y. and Yang, X.
    Proteases for cell suicide: functions and regulation of caspases.
    Microbiol. Mol. Biol. Rev. 64: 821-846 (2000). [PMID: 11104820]
  3. Kang, B.H., Ko, E., Kwon, O.-K. and Choi, K.Y.
    The structure of procaspase 6 is similar to that of active mature caspase 6.
    Biochem. J. 364: 629-634 (2002). [PMID: 12049625]
  4. Lee, S.C., Chan, J., Clement, M.-V. and Pervaiz, S.
    Functional proteomics of resveratrol-induced colon cancer cell apoptosis: caspase-6-mediated cleavage of lamin A is a major signaling loop.
    Proteomics 6: 2386-2394 (2006). [PMID: 16518869]
  5. MacLachlan, T.K. and El-Deiry, W.S.
    Apoptotic threshold is lowered by p53 transactivation of caspase-6.
    Proc. Natl. Acad. Sci. USA 99: 9492-9497 (2002). [PMID: 12089322]
  6. Takahashi, A., Alnemri, E.S., Lazebnik, Y.A., Fernandes-Alnemri, T., Litwack, G., Moir, R.D., Goldman, R.D., Poirier, G.G., Kaufmann, S.H. and Earnshaw, W.C.
    Cleavage of lamin A by Mch2α but not CPP32: multiple interleukin 1β-converting enzyme-related proteases with distinct substrate recognition properties are active in apoptosis.
    Proc. Natl. Acad. Sci. USA 93: 8395-8400 (1996). [PMID: 8710882]

[EC 2.4.22.59 created 2007]