TRAIL-induced apoptosis is independent of the mitochondrial apoptosis mediator DAP3.
Tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis is mediated by its receptors DR4 (TRAIL-R1) and DR5 (TRAIL-R2) and the adapter protein Fas-associated death domain protein (FADD). Recently, an adapter function for death-associated protein 3 (DAP3) between DR4/DR5 and FADD has been proposed. However, DAP3 has been reported to be a ribosomal protein localized to the mitochondrial matrix. To address these discrepancies, the intracellular localization of DAP3 after apoptosis induction in human T-lymphocytes with recombinant TRAIL was analyzed. DAP3, in contrast to cytochrome c, remained intra-mitochondrial during apoptosis. No interaction between FADD and DAP3 after cell fractionation could be detected as long as subcellular compartments remained intact. Only whole cell lysate co-immunoprecipitation revealed an ex vivo interaction between DAP3 and FADD. Therefore, DAP3 and FADD interact only in vitro after disruption of the cellular compartments. TRAIL-induced and DR4-mediated apoptosis in Jurkat cells is independent of DAP3.
D000906:Antibodies; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D002458:Cell Fractionation / Q000379:methods; D003600:Cytosol / Q000502:physiology; D006801:Humans; D007425:Intracellular Membranes / Q000502:physiology; D019169:Jurkat Cells; D007700:Kinetics; D008163:Luminescent Measurements; D008562:Membrane Glycoproteins / Q000502:physiology*; D008928:Mitochondria / Q000502:physiology*; D011506:Proteins / Q000378:metabolism*; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins / Q000378:metabolism; D012269:Ribosomal Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D000906:Antibodies; D051017:Apoptosis Regulatory Proteins; C097041:DAP3 protein, human; D008562:Membrane Glycoproteins; D011506:Proteins; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D012269:Ribosomal Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha