Caspase activation via Death Receptors in the presence of ligand

Stable Identifier
R-HSA-140534
Type
Pathway
Species
Homo sapiens
Compartment
Synonyms
Ligand-dependent caspase activation
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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].

Literature References
PubMed ID Title Journal Year
12620240 Insights into the regulatory mechanism for caspase-8 activation

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

Mol. Cell 2003
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
14644197 Mechanisms of caspase activation

Boatright, KM, Salvesen, GS

Curr Opin Cell Biol 2003
19851329 Studies of the molecular mechanism of caspase-8 activation by solution NMR

Keller, N, Grütter, MG, Zerbe, O

Cell Death Differ. 2010
12620239 A unified model for apical caspase activation

Boatright, KM, Renatus, M, Scott, FL, Sperandio, S, Shin, H, Pedersen, IM, Ricci, JE, Edris, WA, Sutherlin, DP, Green, DR, Salvesen, GS

Mol Cell 2003
Participants
Participant Of
Event Information
Orthologous Events
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Created