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 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. |
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 (2002) 1046–1056. [DOI] [PMID: 12232792] |
2. |
Chang, H.Y. and Yang, X. Proteases for cell suicide: functions and regulation of caspases. Microbiol. Mol. Biol. Rev. 64 (2000) 821–846. [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 (2002) 629–634. [DOI] [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 (2006) 2386–2394. [DOI] [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 (2002) 9492–9497. [DOI] [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 (1996) 8395–8400. [DOI] [PMID: 8710882] |
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