© The Rockefeller University Press,
0021-9525/1998//1353 $5.00
The Journal of Cell Biology, Volume 143, Number 5,
, 1998 1353-1360
Caspase-independent Cell Killing by Fas-associated Protein with Death Domain
Atsuo Kawahara*,
,
Yoshiyuki Ohsawa
,
Hirotaka Matsumura*,
Yasuo Uchiyama
, and
Shigekazu Nagata*,
* Department of Genetics and
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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-
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-
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[Full Text]
-
Kim, S. O., Ono, K., Han, J.
(2001). Apoptosis by pan-caspase inhibitors in lipopolysaccharide-activated macrophages. Am. J. Physiol. Lung Cell. Mol. Physiol.
281: L1095-L1105
[Abstract]
[Full Text]
-
Herr, I., Debatin, K.-M.
(2001). Cellular stress response and apoptosis in cancer therapy. Blood
98: 2603-2614
[Abstract]
[Full Text]
-
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(2001). Tumoricidal Activity of Monocyte-Derived Dendritic Cells: Evidence for a Caspase-8-Dependent, Fas-Associated Death Domain-Independent Mechanism. J. Immunol.
167: 3565-3569
[Abstract]
[Full Text]
-
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(2001). The T Cell Death Knell: Immune-mediated Tumor Death in Renal Cell Carcinoma. Clin. Cancer Res.
7: 3276-3281
[Abstract]
[Full Text]
-
Sung Ouk Kim, , Jiahuai Han,
(2001). Pan-caspase inhibitor zVAD enhances cell death in RAW246.7 macrophages. Innate Immunity
7: 292-296
[Abstract]
-
Foghsgaard, L., Wissing, D., Mauch, D., Lademann, U., Bastholm, L., Boes, M., Elling, F., Leist, M., Jaattela, M.
(2001). Cathepsin B Acts as a Dominant Execution Protease in Tumor Cell Apoptosis Induced by Tumor Necrosis Factor. JCB
153: 999-1010
[Abstract]
[Full Text]
-
Seluanov, A., Gorbunova, V., Falcovitz, A., Sigal, A., Milyavsky, M., Zurer, I., Shohat, G., Goldfinger, N., Rotter, V.
(2001). Change of the Death Pathway in Senescent Human Fibroblasts in Response to DNA Damage Is Caused by an Inability To Stabilize p53. Mol. Cell. Biol.
21: 1552-1564
[Abstract]
[Full Text]
-
Seol, D.-W., Li, J., Seol, M.-H., Park, S.-Y., Talanian, R. V., Billiar, T. R.
(2001). Signaling Events Triggered by Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL): Caspase-8 Is Required for TRAIL-induced Apoptosis. Cancer Res.
61: 1138-1143
[Abstract]
[Full Text]
-
Matsumura, H., Shimizu, Y., Ohsawa, Y., Kawahara, A., Uchiyama, Y., Nagata, S.
(2000). Necrotic Death Pathway in FAS Receptor Signaling. JCB
151: 1247-1256
[Abstract]
[Full Text]
-
Gastman, B. R., Yin, X.-M., Johnson, D. E., Wieckowski, E., Wang, G.-Q., Watkins, S. C., Rabinowich, H.
(2000). Tumor-induced Apoptosis of T Cells: Amplification by a Mitochondrial Cascade. Cancer Res.
60: 6811-6817
[Abstract]
[Full Text]
-
Li, M., Beg, A. A.
(2000). Induction of Necrotic-Like Cell Death by Tumor Necrosis Factor Alpha and Caspase Inhibitors: Novel Mechanism for Killing Virus-Infected Cells. J. Virol.
74: 7470-7477
[Abstract]
[Full Text]
-
Vande Velde, C., Cizeau, J., Dubik, D., Alimonti, J., Brown, T., Israels, S., Hakem, R., Greenberg, A. H.
(2000). BNIP3 and Genetic Control of Necrosis-Like Cell Death through the Mitochondrial Permeability Transition Pore. Mol. Cell. Biol.
20: 5454-5468
[Abstract]
[Full Text]
-
Dumont, C., Durrbach, A., Bidere, N., Rouleau, M., Kroemer, G., Bernard, G., Hirsch, F., Charpentier, B., Susin, S. A., Senik, A.
(2000). Caspase-independent commitment phase to apoptosis in activated blood T lymphocytes: reversibility at low apoptotic insult. Blood
96: 1030-1038
[Abstract]
[Full Text]
-
Costantini, P., Jacotot, E., Decaudin, D., Kroemer, G.
(2000). Mitochondrion as a Novel Target of Anticancer Chemotherapy. JNCI J Natl Cancer Inst
92: 1042-1053
[Abstract]
[Full Text]
-
Sayers, T. J., Brooks, A. D., Seki, N., Smyth, M. J., Yagita, H., Blazar, B. R., Malyguine, A. M.
(2000). T cell lysis of murine renal cancer: multiple signaling pathways for cell death via Fas. J. Leukoc. Biol.
68: 81-86
[Abstract]
[Full Text]
-
Eby, M. T., Jasmin, A., Kumar, A., Sharma, K., Chaudhary, P. M.
(2000). TAJ, a Novel Member of the Tumor Necrosis Factor Receptor Family, Activates the c-Jun N-terminal Kinase Pathway and Mediates Caspase-independent Cell Death. J. Biol. Chem.
275: 15336-15342
[Abstract]
[Full Text]
-
Nadano, D., Sato, T.-A.
(2000). Caspase-3-dependent and -independent Degradation of 28 S Ribosomal RNA May Be Involved in the Inhibition of Protein Synthesis during Apoptosis Initiated by Death Receptor Engagement. J. Biol. Chem.
275: 13967-13973
[Abstract]
[Full Text]
-
Brown, S. B., Clarke, M. C. H., Magowan, L., Sanderson, H., Savill, J.
(2000). Constitutive Death of Platelets Leading to Scavenger Receptor-mediated Phagocytosis. A CASPASE-INDEPENDENT CELL CLEARANCE PROGRAM. J. Biol. Chem.
275: 5987-5996
[Abstract]
[Full Text]
-
Scaffidi, C., Volkland, J., Blomberg, I., Hoffmann, I., Krammer, P. H., Peter, M. E.
(2000). Phosphorylation of FADD/ MORT1 at Serine 194 and Association with a 70-kDa Cell Cycle-Regulated Protein Kinase. J. Immunol.
164: 1236-1242
[Abstract]
[Full Text]
-
Jones, B. E., Lo, C. R., Liu, H., Srinivasan, A., Streetz, K., Valentino, K. L., Czaja, M. J.
(2000). Hepatocytes Sensitized to Tumor Necrosis Factor-alpha Cytotoxicity Undergo Apoptosis through Caspase-dependent and Caspase-independent Pathways. J. Biol. Chem.
275: 705-712
[Abstract]
[Full Text]
-
Drenou, B., Blancheteau, V., Burgess, D. H., Fauchet, R., Charron, D. J., Mooney, N. A.
(1999). A Caspase-Independent Pathway of MHC Class II Antigen-Mediated Apoptosis of Human B Lymphocytes. J. Immunol.
163: 4115-4124
[Abstract]
[Full Text]
-
Boone, E., Vanden Berghe, T., Van Loo, G., De Wilde, G., De Wael, N., Vercammen, D., Fiers, W., Haegeman, G., Vandenabeele, P.
(2000). Structure/Function Analysis of p55 Tumor Necrosis Factor Receptor and Fas-associated Death Domain. EFFECT ON NECROSIS IN L929sA CELLS. J. Biol. Chem.
275: 37596-37603
[Abstract]
[Full Text]
-
Kumar, A., Eby, M. T., Sinha, S., Jasmin, A., Chaudhary, P. M.
(2001). The Ectodermal Dysplasia Receptor Activates the Nuclear Factor-kappa B, JNK, and Cell Death Pathways and Binds to Ectodysplasin A. J. Biol. Chem.
276: 2668-2677
[Abstract]
[Full Text]
-
Kwon, Y.-G., Min, J.-K., Kim, K.-M., Lee, D.-J., Billiar, T. R., Kim, Y.-M.
(2001). Sphingosine 1-Phosphate Protects Human Umbilical Vein Endothelial Cells from Serum-deprived Apoptosis by Nitric Oxide Production. J. Biol. Chem.
276: 10627-10633
[Abstract]
[Full Text]
-
Siegmund, D., Mauri, D., Peters, N., Juo, P., Thome, M., Reichwein, M., Blenis, J., Scheurich, P., Tschopp, J., Wajant, H.
(2001). Fas-associated Death Domain Protein (FADD) and Caspase-8 Mediate Up-regulation of c-Fos by Fas Ligand and Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) via a FLICE Inhibitory Protein (FLIP)-regulated Pathway. J. Biol. Chem.
276: 32585-32590
[Abstract]
[Full Text]
-
Cremesti, A., Paris, F., Grassme, H., Holler, N., Tschopp, J., Fuks, Z., Gulbins, E., Kolesnick, R.
(2001). Ceramide Enables Fas to Cap and Kill. J. Biol. Chem.
276: 23954-23961
[Abstract]
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