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© The Rockefeller University Press, 0021-9525/1998//1353 $5.00
The Journal of Cell Biology, Volume 143, Number 5, , 1998 1353-1360


Article

Caspase-independent Cell Killing by Fas-associated Protein with Death Domain



Atsuo Kawahara*,§, Yoshiyuki Ohsawa{ddagger}, Hirotaka Matsumura*, Yasuo Uchiyama{ddagger}, and Shigekazu Nagata*,§

* Department of Genetics and {ddagger} Department of Anatomy, Osaka University Medical School, Yamada-oka, Suita, Osaka 565-0871, Japan; and § Osaka Bioscience Institute, Furuedai, Suita, Osaka 565-0874, Japan

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.

Key Words: apoptosis • caspase • Fas • Fas-associated protein with death domain • necrosis



Abbreviations used in this paper: FADD, Fas-associated protein with death domain; FKBP, FK506 binding protein; HA, hemagglutinin; PARP, poly(ADP-ribose) polymerase; TNF, tumor necrosis factor.

Dr. Kawahara's present address is Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892.

Address all correspondence to Shigekazu Nagata, Osaka University Medical School, B-3, Department of Genetics, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. Tel.: 81-6-879-3310. Fax: 81-6-879-3319. E-mail: nagata{at}genetic.med.osaka-u.ac.jp



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