Hydrolases;
Acting on peptide bonds (peptidases);
Cysteine endopeptidases

Strict requirement for Asp at position P1 and has a preferred cleavage sequence of Val-Glu-His-Asp!

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 leads 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 the release of cytochrome c 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 fragmentation in the final phases of apoptosis [2,4,5,6]. Belongs in peptidase family C14.

EC 3.4.22.59 created 2007

1  [PMID:12232792]

Cowling V, 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 9:1046-56 (2002)
DOI:10.1038/sj.cdd.4401065

2  [PMID:11104820]

Chang HY, Yang X.

Proteases for cell suicide: functions and regulation of caspases.

Microbiol Mol Biol Rev 64:821-46 (2000)

3  [PMID:12049625]

Kang BH, Ko E, Kwon OK, Choi KY.

The structure of procaspase 6 is similar to that of active mature caspase 6.

Biochem J 364:629-34 (2002)
DOI:10.1042/BJ20011787

4  [PMID:16518869]

Lee SC, Chan J, Clement MV, Pervaiz S.

Functional proteomics of resveratrol-induced colon cancer cell apoptosis: caspase-6-mediated cleavage of lamin A is a major signaling loop.

Proteomics 6:2386-94 (2006)
DOI:10.1002/pmic.200500366

5  [PMID:12089322]

MacLachlan TK, El-Deiry WS.

Apoptotic threshold is lowered by p53 transactivation of caspase-6.

Proc Natl Acad Sci U S A 99:9492-7 (2002)
DOI:10.1073/pnas.132241599

6  [PMID:8710882]

Takahashi A, Alnemri ES, Lazebnik YA, Fernandes-Alnemri T, Litwack G, Moir RD, Goldman RD, Poirier GG, Kaufmann SH, Earnshaw WC.

Cleavage of lamin A by Mch2 alpha but not CPP32: multiple interleukin 1 beta-converting enzyme-related proteases with distinct substrate recognition properties are active in apoptosis.

Proc Natl Acad Sci U S A 93:8395-400 (1996)
DOI:10.1073/pnas.93.16.8395