EC 3.4.22.61 - Caspase-8

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IntEnz Enzyme Nomenclature
EC 3.4.22.61

Names

Accepted name:
caspase-8
Other names:
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
Systematic name:
-

Reaction

Comments:

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, which 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.

Links to other databases

Enzymes and pathways: NC-IUBMB , BRENDA , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , MEROPS , UniPathway
Protein domains and families: PROSITE:PDOC00864
Structural data: CSA , EC2PDB
UniProtKB/Swiss-Prot:

References

  1. Chang, H.Y. and Yang, X.
    Proteases for cell suicide: functions and regulation of caspases.
    Microbiol. Mol. Biol. Rev. 64: 821-846 (2000). [PMID: 11104820]
  2. Boldin, M.P., Goncharov, T.M., Goltsev, Y.V. and Wallach, D.
    Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death.
    Cell 85: 803-815 (1996). [PMID: 8681376]
  3. Muzio, M., Chinnaiyan, A.M., Kischkel, F.C., O'Rourke, K., Shevchenko, A., Ni, J., Scaffidi, C., Bretz, J.D., Zhang, M., Gentz, R., Mann, M., Krammer, P.H., Peter, M.E. and Dixit, V.M.
    FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex.
    Cell 85: 817-827 (1996). [PMID: 8681377]
  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, 1293-1296
  5. Fischer, U., Stroh, C. and Schulze-Osthoff, K.
    Unique and overlapping substrate specificities of caspase-8 and caspase-10.
    Oncogene 25: 152-159 (2006). [PMID: 16186808]
  6. Blanchard, H., Donepudi, M., Tschopp, M., Kodandapani, L., Wu, J.C., Grütter, M.G.
    Caspase-8 specificity probed at subsite S4: crystal structure of the caspase-8-Z-DEVD-cho complex.
    J. Mol. Biol. 302: 9-16 (2000). [PMID: 10964557]
  7. Boatright, K.M., Deis, C., Denault, J.-B., Sutherlin, D.P. and Salvesen, G.S.
    Activation of caspases-8 and -10 by FLIPL.
    Biochem. J. 382: 651-657 (2004). [PMID: 15209560]

[EC 3.4.22.61 created 2007]