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Caspase-3 is a component of Fas death-inducing signaling complex in lipid rafts and its activity is required for complete caspase-8 activation during Fas-mediated cell death
Journal article   Open access   Peer reviewed

Caspase-3 is a component of Fas death-inducing signaling complex in lipid rafts and its activity is required for complete caspase-8 activation during Fas-mediated cell death

Salah M Aouad, Luchino Y Cohen, Ehsan Sharif-Askari, Elias K Haddad, Antoine Alam and Rafick-Pierre Sekaly
The Journal of immunology (1950), v 172(4), pp 2316-2323
15 Feb 2004
DOI: https://doi.org/10.4049/jimmunol.172.4.2316
PMID: 14764700
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
http://www.jimmunol.org/content/172/4/2316.full.pdfView
Published, Version of Record (VoR) Open
url
https://doi.org/10.4049/jimmunol.172.4.2316View
Published, Version of Record (VoR) Open

Abstract

Abridged Index Medicus
Since its discovery, caspase-8 has been placed at the apex of the proteolytic cascade triggered by death receptor (DR) cross-linking. Because of its capacity to interact with the cytoplasmic portion of DR, it has been suggested that caspase-8 acts independently of other caspases in the initiation of Fas and other DR signaling. In this study, we demonstrate that in Jurkat cells, caspase-3 cleavage is an early step during Fas-induced apoptosis. We show that caspase-3 processing into its p20 occurs rapidly after Fas cross-linking, in the absence of mitochondrial depolarization and caspase-9 activation. Moreover, caspase-3 is present in lipid rafts of untreated Jurkat cells and peripheral T lymphocytes. Caspase-3, caspase-8, and Fas-associated death domain are further recruited to lipid rafts of Jurkat cells following anti-Fas treatment. Fas immunoprecipitation reveals that caspase-3 is a component of the death-inducing signaling complex, suggesting that this cysteine protease is in close proximity to caspase-8. Furthermore, transduction of Jurkat cells with a caspase-3 dominant-negative form inhibits caspase-8 processing and results in inhibition of apoptosis, suggesting that caspase-3 activity is required for caspase-8 activation. Overall, these findings support a model whereby caspase-3 is a component of the death-inducing signaling complex located in lipid rafts, and as such, is involved in the amplification of caspase-8 activity by the mitochondrion.

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Collaboration types
Domestic collaboration
Web of Science research areas
Immunology
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