Caspase 7 Explained

Caspase-7, apoptosis-related cysteine peptidase, also known as CASP7, is a human protein encoded by the CASP7 gene.CASP7 orthologs^[1] have been identified in nearly all mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts.

Function

Caspase-7 is a member of the caspase (cysteine aspartate protease) family of proteins, and has been shown to be an executioner protein of apoptosis. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes that undergo proteolytic processing by upstream caspases (caspase-8, -9) at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme in the form of a heterotetramer. The precursor of this caspase is cleaved by caspase 3, caspase 10, and caspase 9. It is activated upon cell death stimuli and induces apoptosis. Alternative splicing results in four transcript variants, encoding three distinct isoforms.^[2]

Interactions

Caspase 7 has been shown to interact with:

• Caspase 8,^{[3] [4]}
• Survivin^{[5] [6]} and
• XIAP.^{[7] [8] [9] [10]}

See also

• The Proteolysis Map
• Caspase

Further reading

• Cohen GM . Caspases: the executioners of apoptosis . Biochem. J. . 326 . Pt 1 . 1–16 . 1997 . 9337844 . 1218630 . 10.1042/bj3260001.

External links

• The MEROPS online database for peptidases and their inhibitors: C14.004

Notes and References

1. Web site: OrthoMaM phylogenetic marker: CASP7 coding sequence . 2009-12-20 . https://web.archive.org/web/20160304031521/http://www.orthomam.univ-montp2.fr/orthomam/data/cds/detailMarkers/ENSG00000165806_CASP7.xml . 2016-03-04 . dead .
2. Web site: Entrez Gene: CASP7 caspase 7, apoptosis-related cysteine peptidase.
3. Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T, Alnemri ES . Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria . J. Biol. Chem. . 277 . 16 . 13430–7 . Apr 2002 . 11832478 . 10.1074/jbc.M108029200 . free .
4. Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri ES . 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 . Dec 1996 . 8962078 . 26159 . 10.1073/pnas.93.25.14486. 1996PNAS...9314486S . free .
5. Tamm I, Wang Y, Sausville E, Scudiero DA, Vigna N, Oltersdorf T, Reed JC . IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs . Cancer Res. . 58 . 23 . 5315–20 . Dec 1998 . 9850056 .
6. Shin S, Sung BJ, Cho YS, Kim HJ, Ha NC, Hwang JI, Chung CW, Jung YK, Oh BH . An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7 . Biochemistry . 40 . 4 . 1117–23 . Jan 2001 . 11170436 . 10.1021/bi001603q.
7. Riedl SJ, Renatus M, Schwarzenbacher R, Zhou Q, Sun C, Fesik SW, Liddington RC, Salvesen GS . Structural basis for the inhibition of caspase-3 by XIAP . Cell . 104 . 5 . 791–800 . Mar 2001 . 11257232 . 10.1016/S0092-8674(01)00274-4. 17915093 . free .
8. Roy N, Deveraux QL, Takahashi R, Salvesen GS, Reed JC . The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases . EMBO J. . 16 . 23 . 6914–25 . Dec 1997 . 9384571 . 1170295 . 10.1093/emboj/16.23.6914 .
9. Deveraux QL, Takahashi R, Salvesen GS, Reed JC . X-linked IAP is a direct inhibitor of cell-death proteases . Nature . 388 . 6639 . 300–4 . Jul 1997 . 9230442 . 10.1038/40901 . 1997Natur.388..300D . 4395885 . free .
10. Suzuki Y, Nakabayashi Y, Nakata K, Reed JC, Takahashi R . X-linked inhibitor of apoptosis protein (XIAP) inhibits caspase-3 and -7 in distinct modes . J. Biol. Chem. . 276 . 29 . 27058–63 . Jul 2001 . 11359776 . 10.1074/jbc.M102415200 . free .