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

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