caspase-3;
CPP32;
apopain;
yama protein

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

Strict requirement for an Asp residue at positions P1 and P4. It has a preferred cleavage sequence of Asp-Xaa-Xaa-Asp! with a hydrophobic amino-acid residue at P2 and a hydrophilic amino-acid residue at P3, although Val or Ala are also accepted at this position

Caspase-3 is an effector/executioner caspase, as are caspase-6 (EC 3.4.22.59) and caspase-7 (EC 3.4.22.60) [5]. 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 [3,5]. Procaspase-3 can be activated by caspase-1 (EC 3.4.22.36), caspase-8 (EC 3.4.22.61), caspase-9 (EC 3.4.22.62) and caspase-10 (EC 3.4.22.63) as well as by the serine protease granzyme B [1]. Caspase-3 can activate procaspase-2 (EC 3.4.22.55) [2]. Activation occurs by inter-domain cleavage followed by removal of the N-terminal prodomain [6]. Although Asp-Glu-(Val/Ile)-Asp is thought to be the preferred cleavage sequence, the enzyme can accommodate different residues at P2 and P3 of the substrate [4]. Like caspase-2, a hydrophobic residue at P5 of caspase-3 leads to more efficient hydrolysis, e.g. (Val/Leu)-Asp-Val-Ala-Asp! is a better substrate than Asp-Val-Ala-Asp! . This is not the case for caspase-7 [4]. Belongs in peptidase family C14.

1  [PMID:11123933]

Krebs JF, Srinivasan A, Wong AM, Tomaselli KJ, Fritz LC, Wu JC.

Heavy membrane-associated caspase 3: identification, isolation, and characterization.

Biochemistry. 39 (2000) 16056-63.

2  [PMID:9261102]

Li H, Bergeron L, Cryns V, Pasternack MS, Zhu H, Shi L, Greenberg A, Yuan J.

Activation of caspase-2 in apoptosis.

J. Biol. Chem. 272 (1997) 21010-7.

3

Nicholson, D. and Thornberry, N.A.

Caspase-3 and caspase-7.

In: Barrett, A.J., Rawlings, N.D. and Woessner, J.F. (Eds.), Handbook of Proteolytic Enzymes, 2nd ed., Elsevier, London, 2004, p. 1298-1302.

4  [PMID:16781734]

Fang B, Boross PI, Tozser J, Weber IT.

Structural and kinetic analysis of caspase-3 reveals role for s5 binding site in substrate recognition.

J. Mol. Biol. 360 (2006) 654-66.

5  [PMID:11104820]

Chang HY, Yang X.

Proteases for cell suicide: functions and regulation of caspases.

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

6  [PMID:8665848]

Martin SJ, Amarante-Mendes GP, Shi L, Chuang TH, Casiano CA, O'Brien GA, Fitzgerald P, Tan EM, Bokoch GM, Greenberg AH, Green DR.

The cytotoxic cell protease granzyme B initiates apoptosis in a cell-free system by proteolytic processing and activation of the ICE/CED-3 family protease, CPP32, via a novel two-step mechanism.

EMBO. J. 15 (1996) 2407-16.