caspase-8;
FLICE, FADD-like ICE;
MACH;
MORT1-associated CED-3 homolog;
Mch5;
mammalian Ced-3 homolog 5;
CASP-8;
ICE-like apoptotic protease 5;
FADD-homologous ICE/CED-3-like protease;
apoptotic cysteine protease;
apoptotic protease Mch-5;
CAP4

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

Strict requirement for Asp at position P1 and has a preferred cleavage sequence of (Leu/Asp/Val)-Glu-Thr-Asp!(Gly/Ser/Ala)

Caspase-8 is an initiator caspase, as are caspase-2 (EC 3.4.22.55), caspase-9 (EC 3.4.22.62) and caspase-10 (EC 3.4.22.63) [1]. Caspase-8 is the apical activator of the extrinsic (death receptor) apoptosis pathway, triggered by death receptor ligation [2]. It contains two tandem death effector domains (DEDs) in its N-terminal prodomain, and these play a role in procaspase activation [1]. This enzyme is linked to cell surface death receptors such as Fas [1,5]. When Fas is aggregated by the Fas ligand, procaspase-8 is recruited to the death receptor where it is activated [1]. The enzyme has a preference for Glu at P3 and prefers small residues, such as Gly, Ser and Ala, at the P1' position. It has very broad P4 specificity, tolerating substrates with Asp, Val or Leu in this position [2,3,4]. Endogenous substrates for caspase-8 include procaspase-3, the pro-apoptotic Bcl-2 family member Bid, RIP, PAK2 and the caspase-8 activity modulator FLIPL [4,5]. Belongs in peptidase family C14.

1  [PMID:11104820]

Chang HY, Yang X.

Proteases for cell suicide: functions and regulation of caspases.

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

2  [PMID:8681376]

Boldin MP, Goncharov TM, Goltsev YV, Wallach D.

Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death.

Cell. 85 (1996) 803-15.

3  [PMID:8681377]

Muzio M, Chinnaiyan AM, Kischkel FC, O'Rourke K, Shevchenko A, Ni J, Scaffidi C, Bretz JD, Zhang M, Gentz R, Mann M, Krammer PH, Peter ME, Dixit VM.

FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death--inducing signaling complex.

Cell. 85 (1996) 817-27.

4

Salvesen, G.S. and Boatright, K.M.

Caspase-8.

In: Barrett, A.J., Rawlings, N.D. and Woessner, J.F. (Eds.), Handbook of Proteolytic Enzymes, 2nd ed., Elsevier, London, 2004, p. 1293-1296.

5  [PMID:16186808]

Fischer U, Stroh C, Schulze-Osthoff K.

Unique and overlapping substrate specificities of caspase-8 and caspase-10.

Oncogene. 25 (2006) 152-9.

6  [PMID:10964557]

Blanchard H, Donepudi M, Tschopp M, Kodandapani L, Wu JC, Grutter MG.

Caspase-8 specificity probed at subsite S(4): crystal structure of the caspase-8-Z-DEVD-cho complex.

J. Mol. Biol. 302 (2000) 9-16.

7  [PMID:15209560]

Boatright KM, Deis C, Denault JB, Sutherlin DP, Salvesen GS.

Activation of caspases-8 and -10 by FLIP(L).

Biochem. J. 382 (2004) 651-7.