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PMID: 9832562 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Caspase-independent cell killing by Fas-associated protein with death domain.

The Journal of cell biology ·Vol. 143 ·No. 5 ·1998-11-30 ·Pages 1353-60

Kawahara A, Ohsawa Y, Matsumura H, Uchiyama Y, Nagata S

Abstract

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.

MeSH Terms
Adaptor Proteins, Signal Transducing Apoptosis/physiology Carrier Proteins/chemistry,genetics,metabolism Caspase 8 Caspase 9 Caspases/metabolism Cell Death/physiology Cell Line, Transformed Fas Ligand Protein Fas-Associated Death Domain Protein Humans Immunophilins/genetics,metabolism Jurkat Cells Membrane Glycoproteins/metabolism Microscopy, Electron Necrosis Protein Conformation Tacrolimus Binding Proteins fas Receptor/metabolism
Chemicals
Adaptor Proteins, Signal Transducing Carrier Proteins FADD protein, human FASLG protein, human Fas Ligand Protein Fas-Associated Death Domain Protein Membrane Glycoproteins fas Receptor CASP8 protein, human CASP9 protein, human Caspase 8 Caspase 9 Caspases Tacrolimus Binding Proteins Immunophilins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kawahara A
Department of Genetics, Osaka University Medical School, Yamada-oka, Suita, Osaka 565-0871, Japan.
Ohsawa Y
Matsumura H
Uchiyama Y
Nagata S
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.143.5.1353
Published
1998-11-30
Pages
1353-60
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2133085
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.143.5.1353 PMC Full Text View journal details
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