Caspase-8 processing in the DISC

Stable Identifier
R-HSA-139952
Type
Reaction [omitted]
Species
Homo sapiens
Related Species
Molluscum contagiosum virus subtype 1, Human herpesvirus 8
Compartment
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Caspase-8 zymogens are present in the cells as inactive monomers, containing a large N-terminal prodomain with two death effector domains (DED), and a C-terminal catalytic subunit composed of small and a large domains separated by a smaller linker region [Donepudi M et al 2003; Keller N et al 2009]. Dimerization is required for the caspase-8 activation [Donepudi M et al 2003]. Once dimerized, caspase-8 zymogen undergoes a series of autoproteolytic cleavage events at aspartic acid residues in their interdomain linker regions. A second cleavage event between the the N-terminal prodomain and the catalytic domain releases the active caspase from the activation complex into the cytosol. The resulting fully active enzyme is a homodimer of catalytic domains, where each domain is composed of a large p18 and a small p10 subunit [Keller N et al 2009; Oberst A et al 2010].

Literature References
PubMed ID Title Journal Year
20308068 Inducible dimerization and inducible cleavage reveal a requirement for both processes in caspase-8 activation

Oberst, A, Pop, C, Tremblay, AG, Blais, V, Denault, JB, Salvesen, GS, Green, DR

J Biol Chem 2010
19278658 Structural and biochemical studies on procaspase-8: new insights on initiator caspase activation

Keller, N, Mares, J, Zerbe, O, Grütter, MG

Structure 2009
12620240 Insights into the regulatory mechanism for caspase-8 activation

Donepudi, M, Mac Sweeney, A, Briand, C, Grütter, MG

Mol. Cell 2003
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
cysteine-type endopeptidase activity of active caspase-8 [cytosol]
Physical Entity
Activity
This event is regulated
Reviewed
Created