Ligand-dependent caspase activation (R-HSA-140534) [Homo sapiens]


Caspase-8 is synthesized as zymogen (procaspase-8) and is formed from procaspase-8 as a cleavage product. However, the cleavage itself appears not to be sufficient for the formation of an active caspase-8. Only the coordinated dimerization and cleavage of the zymogen produce efficient activation in vitro and apoptosis in cellular systems [Boatright KM and Salvesen GS 2003; Keller N et al 2010; Oberst A et al 2010].

The caspase-8 zymogens are present in the cells as inactive monomers, which are recruited to the death-inducing signaling complex (DISC) by homophilic interactions with the DED domain of FADD. The monomeric zymogens undergo dimerization and the subsequent conformational changes at the receptor complex, which results in the formation of catalytically active form of procaspase-8.[Boatright KM et al 2003; Donepudi M et al 2003; Keller N et al 2010; Oberst A et al 2010].

Locations in the PathwayBrowser
Additional Information
Compartment cytosol
GO Biological Process activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway (0097296)
Cross References
Database Identifier
BioModels Database BIOMD0000000243, BIOMD0000000523, BIOMD0000000525, BIOMD0000000526, BIOMD0000000407, BIOMD0000000524, BIOMD0000000220
Literature References
pubMedId Title Journal Year
14644197 Mechanisms of caspase activation Curr Opin Cell Biol 2003
20308068 Inducible dimerization and inducible cleavage reveal a requirement for both processes in caspase-8 activation J Biol Chem 2010
12620239 A unified model for apical caspase activation Mol Cell 2003
19851329 Studies of the molecular mechanism of caspase-8 activation by solution NMR Cell Death Differ. 2010
12620240 Insights into the regulatory mechanism for caspase-8 activation Mol. Cell 2003
Inferred Entries
Orthologous events