J. Cell Biol.
© The Rockefeller University Press
0021-9525/97/04/221/09 $2.00
Volume 137, Number 1, April 7, 1997 221-229

Interleukin 1-converting Enzyme Related Proteases/Caspases Are Involved in TRAIL-induced Apoptosis of Myeloma and Leukemia Cells

Sara M. Mariani, Bernd Matiba, Elena A. Armandola,^* and Peter H. Krammer

Tumor Immunology and ^* Molecular Immunology Program/Division of Immunogenetics, German Cancer Research Center, Heidelberg, Germany

The Fas/APO-1/CD95 ligand (CD95L) and the recently cloned TRAIL ligand belong to the TNFfamily and share the ability to induce apoptosis in sensitive target cells. Little information is available on the degree of functional redundancy between these two ligands in terms of target selectivity and intracellular signalling pathway(s). To address these issues, we have expressed and characterized recombinant mouse TRAIL. Specific detection with newly developed rabbit anti-TRAIL antibodies showed that the functional TRAIL molecule released into the supernatant of recombinant baculovirus-infected Sf9 cells is very similar to that associated with the membrane fraction of Sf9 cells. CD95L resistant myeloma cells were found to be sensitive to TRAIL, displaying apoptotic features similar to those of the CD95L- and TRAIL-sensitive T leukemia cells Jurkat. To assess if IL-1-converting enzyme (ICE) and/or ICE-related proteases (IRPs) (caspases) are involved in TRAIL-induced apoptosis of both cell types, peptide inhibition experiments were performed. The irreversible IRP/caspase-inhibitor AcYVAD-cmk and the reversible IRP/caspase-inhibitor Ac-DEVD-CHO blocked the morphological changes, disorganization of plasma membrane phospholipids, DNA fragmentation, and loss of cell viability associated with TRAIL-induced apoptosis. In addition, cells undergoing TRAIL-mediated apoptosis displayed cleavage of poly(ADP)-ribose polymerase (PARP) that was completely blocked by Ac-DEVD-CHO.

These results indicate that TRAIL seems to complement the activity of the CD95 system as it allows cells, otherwise resistant, to undergo apoptosis triggered by specific extracellular ligands. Conversely, however, induction of apoptosis in sensitive cells by TRAIL involves IRPs/caspases in a fashion similar to CD95L. Thus, differential sensitivity to CD95L and TRAIL seems to map to the proximal signaling events associated with receptor triggering.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Carlo-Stella, C., Lavazza, C., Locatelli, A., Vigano, L., Gianni, A. M., Gianni, L. (2007). Targeting TRAIL Agonistic Receptors for Cancer Therapy. Clin. Cancer Res. 13: 2313-2317 [Abstract] [Full Text]  
• Shiraishi, T., Yoshida, T., Nakata, S., Horinaka, M., Wakada, M., Mizutani, Y., Miki, T., Sakai, T. (2005). Tunicamycin Enhances Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Induced Apoptosis in Human Prostate Cancer Cells. Cancer Res. 65: 6364-6370 [Abstract] [Full Text]  
• Riley, J. K., Heeley, J. M., Wyman, A. H., Schlichting, E. L., Moley, K. H. (2004). TRAIL and KILLER Are Expressed and Induce Apoptosis in the Murine Preimplantation Embryo. Biol. Reprod. 71: 871-877 [Abstract] [Full Text]  
• Lee, Y. J., Froelich, C. J., Fujita, N., Tsuruo, T., Kim, J. H. (2004). Reconstitution of Caspase-3 Confers Low Glucose-Enhanced Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Cytotoxicity and Akt Cleavage. Clin. Cancer Res. 10: 1894-1900 [Abstract] [Full Text]  
• Ray, S., Almasan, A. (2003). Apoptosis Induction in Prostate Cancer Cells and Xenografts by Combined Treatment with Apo2 Ligand/Tumor Necrosis Factor-related Apoptosis-inducing Ligand and CPT-11. Cancer Res. 63: 4713-4723 [Abstract] [Full Text]  
• Kim, J. H., Ajaz, M., Lokshin, A., Lee, Y. J. (2003). Role of Antiapoptotic Proteins in Tumor Necrosis Factor-related Apoptosis-inducing Ligand and Cisplatin-augmented Apoptosis. Clin. Cancer Res. 9: 3134-3141 [Abstract] [Full Text]  
• Silvestris, F., Cafforio, P., Tucci, M., Dammacco, F. (2002). Negative regulation of erythroblast maturation by Fas-L+/TRAIL+ highly malignant plasma cells: a major pathogenetic mechanism of anemia in multiple myeloma. Blood 99: 1305-1313 [Abstract] [Full Text]  
• Tollefson, A. E., Toth, K., Doronin, K., Kuppuswamy, M., Doronina, O. A., Lichtenstein, D. L., Hermiston, T. W., Smith, C. A., Wold, W. S. M. (2001). Inhibition of TRAIL-Induced Apoptosis and Forced Internalization of TRAIL Receptor 1 by Adenovirus Proteins. J. Virol. 75: 8875-8887 [Abstract] [Full Text]  
• Vidalain, P.-O., Azocar, O., Yagita, H., Rabourdin-Combe, C., Servet-Delprat, C. (2001). Cytotoxic Activity of Human Dendritic Cells Is Differentially Regulated by Double-Stranded RNA and CD40 Ligand. J. Immunol. 167: 3765-3772 [Abstract] [Full Text]  
• Chen, Q., Gong, B., Mahmoud-Ahmed, A. S., Zhou, A., Hsi, E. D., Hussein, M., Almasan, A. (2001). Apo2L/TRAIL and Bcl-2-related proteins regulate type I interferon-induced apoptosis in multiple myeloma. Blood 98: 2183-2192 [Abstract] [Full Text]  
• Matsushima, T., Nakashima, M., Oshima, K., Abe, Y., Nishimura, J., Nawata, H., Watanabe, T., Muta, K. (2001). Receptor binding cancer antigen expressed on SiSo cells, a novel regulator of apoptosis of erythroid progenitor cells. Blood 98: 313-321 [Abstract] [Full Text]  
• Matsuzaki, H., Schmied, B. M., Ulrich, A., Standop, J., Schneider, M. B., Batra, S. K., Picha, K. S., Pour, P. M. (2001). Combination of Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) and Actinomycin D Induces Apoptosis Even in TRAIL-resistant Human Pancreatic Cancer Cells. Clin. Cancer Res. 7: 407-414 [Abstract] [Full Text]  
• Gong, B., Almasan, A. (2000). Apo2 Ligand/TNF-related Apoptosis-inducing Ligand and Death Receptor 5 Mediate the Apoptotic Signaling Induced by Ionizing Radiation in Leukemic Cells. Cancer Res. 60: 5754-5760 [Abstract] [Full Text]  
• Albon, J., Tullo, A. B., Aktar, S., Boulton, M. E. (2000). Apoptosis in the Endothelium of Human Corneas for Transplantation. IOVS 41: 2887-2893 [Abstract] [Full Text]  
• Zamai, L., Secchiero, P., Pierpaoli, S., Bassini, A., Papa, S., Alnemri, E. S., Guidotti, L., Vitale, M., Zauli, G. (2000). TNF-related apoptosis-inducing ligand (TRAIL) as a negative regulator of normal human erythropoiesis. Blood 95: 3716-3724 [Abstract] [Full Text]  
• Leverkus, M., Neumann, M., Mengling, T., Rauch, C. T., Bröcker, E.-B., Krammer, P. H., Walczak, H. (2000). Regulation of Tumor Necrosis Factor-related Apoptosis-inducing Ligand Sensitivity in Primary and Transformed Human Keratinocytes. Cancer Res. 60: 553-559 [Abstract] [Full Text]  
• Kothny-Wilkes, G., Kulms, D., Luger, T. A., Kubin, M., Schwarz, T. (1999). Interleukin-1 Protects Transformed Keratinocytes from Tumor Necrosis Factor-related Apoptosis-inducing Ligand- and CD95-induced Apoptosis but Not from Ultraviolet Radiation-induced Apoptosis. J. Biol. Chem. 274: 28916-28921 [Abstract] [Full Text]  
• Baker, J. R. Jr. (1999). Editorial: Dying (Apoptosing?) for a Consensus on the Fas Death Pathway in the Thyroid. J. Clin. Endocrinol. Metab. 84: 2593-2595 [Full Text]  
• Costanzo, A., Guiet, C., Vito, P. (1999). c-E10 Is a Caspase-recruiting Domain-containing Protein That Interacts with Components of Death Receptors Signaling Pathway and Activates Nuclear Factor-kappa B. J. Biol. Chem. 274: 20127-20132 [Abstract] [Full Text]  
• Mori, S., Murakami-Mori, K., Nakamura, S., Ashkenazi, A., Bonavida, B. (1999). Sensitization of AIDS-Kaposi's Sarcoma Cells to Apo-2 Ligand-Induced Apoptosis by Actinomycin D. J. Immunol. 162: 5616-5623 [Abstract] [Full Text]  
• Strater, J., Mariani, S. M., Walczak, H., Rucker, F. G., Leithauser, F., Krammer, P. H., Moller, P. (1999). CD95 Ligand (CD95L) in Normal Human Lymphoid Tissues : A Subset of Plasma Cells Are Prominent Producers of CD95L. Am. J. Pathol. 154: 193-201 [Abstract] [Full Text]  
• Lieberthal, W., Triaca, V., Koh, J. S., Pagano, P. J., Levine, J. S. (1998). Role of superoxide in apoptosis induced by growth factor withdrawal. Am. J. Physiol. Renal Physiol. 275: F691-F702 [Abstract] [Full Text]  
• Kothny-Wilkes, G., Kulms, D., Poppelmann, B., Luger, T. A., Kubin, M., Schwarz, T. (1998). Interleukin-1 Protects Transformed Keratinocytes from Tumor Necrosis Factor-related Apoptosis-inducing Ligand. J. Biol. Chem. 273: 29247-29253 [Abstract] [Full Text]  
• Berndt, C., Mopps, B., Angermuller, S., Gierschik, P., Krammer, P. H. (1998). CXCR4 and CD4 mediate a rapid CD95-independent cell death in CD4+ T cells. Proc. Natl. Acad. Sci. USA 95: 12556-12561 [Abstract] [Full Text]  
• Thomas, W. D., Hersey, P. (1998). TNF-Related Apoptosis-Inducing Ligand (TRAIL) Induces Apoptosis in Fas Ligand-Resistant Melanoma Cells and Mediates CD4 T Cell Killing of Target Cells. J. Immunol. 161: 2195-2200 [Abstract] [Full Text]  
• Ashkenazi, A., Dixit, V. M. (1998). Death Receptors: Signaling and Modulation. Science 281: 1305-1308 [Abstract] [Full Text]  
• Chlichlia, K., Peter, M. E., Rocha, M., Scaffidi, C., Bucur, M., Krammer, P. H., Schirrmacher, V., Umansky, V. (1998). Caspase Activation Is Required for Nitric Oxide-Mediated, CD95(APO-1/Fas)-Dependent and Independent Apoptosis in Human Neoplastic Lymphoid Cells. Blood 91: 4311-4320 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents