Caspase-independent cell killing by Fas-associated protein with death domain.
The binding of Fas ligand to Fas recruits caspase 8 to Fas via an adaptor, FADD/MORT1, and activates a caspase cascade leading to apoptosis. Here, we describe a human Jurkat-derived cell line (JB-6) that is deficient in caspase 8. This cell line was resistant to the apoptosis triggered by Fas engagement. However, the multimerization of Fas-associated protein with death domain, through the use of a dimerizing system, killed the JB-6 cells. This killing process was not accompanied by the activation of caspases or DNA fragmentation. The dying cells showed neither condensation nor fragmentation of cells and nuclei, but the cells and nuclei swelled in a manner similar to that seen in necrosis. These results suggested that Fas-associated protein with death domain can kill the cells via two pathways, one mediated by caspases and another that does not involve them.
Kawahara
A
A
Department of Genetics, Osaka University Medical School, Yamada-oka, Suita, Osaka 565-0871, Japan.
Ohsawa
Y
Y
Matsumura
H
H
Uchiyama
Y
Y
Nagata
S
S
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000502:physiology*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D002461:Cell Line, Transformed; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D006801:Humans; D020104:Immunophilins / Q000235:genetics / Q000378:metabolism; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000378:metabolism; D008854:Microscopy, Electron; D009336:Necrosis; D011487:Protein Conformation; D022021:Tacrolimus Binding Proteins; D019014:fas Receptor / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C505533:FADD protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D022021:Tacrolimus Binding Proteins; D020104:Immunophilins