Reactome | Caspase activation via Death Receptors in the presence of ligand

Caspase activation via Death Receptors in the presence of ligand

Stable Identifier

R-HSA-140534

DOI

10.3180/REACT_1503.5

Type

Pathway

Species

Homo sapiens

Compartment

cytosol

Synonyms

Ligand-dependent caspase activation

ReviewStatus

5/5

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Caspase activation via Death Receptors in the presence of ligand

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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
20308068	Inducible dimerization and inducible cleavage reveal a requirement for both processes in caspase-8 activation Blais, V, Oberst, A, Denault, JB, Green, DR, Salvesen, GS, Tremblay, AG, Pop, C	J Biol Chem	2010
12620240	Insights into the regulatory mechanism for caspase-8 activation Grütter, MG, Briand, C, Mac Sweeney, A, Donepudi, M	Mol. Cell	2003
14644197	Mechanisms of caspase activation Salvesen, GS, Boatright, KM	Curr Opin Cell Biol	2003
19851329	Studies of the molecular mechanism of caspase-8 activation by solution NMR Grütter, MG, Keller, N, Zerbe, O	Cell Death Differ.	2010
12620239	A unified model for apical caspase activation Sperandio, S, Shin, H, Ricci, JE, Scott, FL, Renatus, M, Sutherlin, DP, Salvesen, GS, Edris, WA, Boatright, KM, Green, DR, Pedersen, IM	Mol Cell	2003