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
| Autor: | Rafick-Pierre Sekaly, Antoine Alam, Luchino Y. Cohen, Ehsan Sharif-Askari, Salah M. Aouad, Elias K. Haddad |
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| Rok vydání: | 2004 |
| Předmět: |
Death Domain Receptor Signaling Adaptor Proteins
Fas Ligand Protein T-Lymphocytes Immunology Apoptosis Caspase 3 Ligands Caspase 8 Jurkat cells Receptors Tumor Necrosis Factor Membrane Potentials Jurkat Cells Membrane Microdomains Humans Immunology and Allergy fas Receptor Lipid raft Caspase Death domain Membrane Glycoproteins biology Hydrolysis Intracellular Membranes Fas receptor Mitochondria Cell biology Enzyme Activation Caspases biology.protein Protein Processing Post-Translational Signal Transduction |
| Zdroj: | The Journal of Immunology. 172:2316-2323 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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