Inhibition of Fas-induced apoptosis by Bcl-2.
Jurkat cells express Fas, and rapidly undergo apoptosis in response to Fas ligand or an agonistic anti-Fas antibody. This apoptotic pathway is mediated by a cascade of caspases. In this report, we show that Fas activation induced the processing of caspase 8 in Jurkat cells with a time frame similar to the activation of caspase 3 and the proteolysis of nuclear proteins. Jurkat cell transformants that overexpress Bcl-2 were partially but not completely resistant to the Fas-induced apoptosis. Little processing of caspase 8 was observed upon Fas activation in these transformants. Furthermore, although caspase 8 was recruited to Fas upon Fas activation in the parental Jurkat cells, the recruitment of caspase 8 to Fas was inhibited in the transformants overexpressing Bcl-2. These results suggest that Bcl-2 inhibits Fas-induced apoptosis by preventing the formation of the death-inducing signaling complex that is composed of Fas, FADD/MORT1, and caspase 8.
Kawahara
A
A
Osaka Bioscience Institute, Suita, Japan.
Kobayashi
T
T
Nagata
S
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001692:Biological Transport; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D053222:Fas Ligand Protein; D019254:Genes, bcl-2; D006801:Humans; D019169:Jurkat Cells; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D051379:Mice; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014162:Transfection; D019014:fas Receptor / Q000187:drug effects* / Q000502:physiology
D004792:Enzyme Precursors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D019014:fas Receptor; C505530:CASP8 protein, human; C506433:CASP9 protein, human; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases