This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Livne, A.
Right arrow Articles by Kleinberger, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Livne, A.
Right arrow Articles by Kleinberger, T.

 Previous Article  |  Next Article 

Journal of Virology, January 2001, p. 789-798, Vol. 75, No. 2
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.2.789-798.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Caspase Activation by Adenovirus E4orf4 Protein Is Cell Line Specific and Is Mediated by the Death Receptor Pathway

Adi Livne, Ronit Shtrichman,dagger and Tamar Kleinberger*

The Gonda Center of Molecular Microbiology, The Bruce Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel

Received 10 July 2000/Accepted 10 October 2000

Adenovirus E4orf4 protein has been shown to induce transformed cell-specific, protein phosphatase 2A-dependent, and p53-independent apoptosis. It has been further reported that the E4orf4 apoptotic pathway is caspase-independent in CHO cells. Here, we show that E4orf4 induces caspase activation in the human cell lines H1299 and 293T. Caspase activation is required for apoptosis in 293T cells, but not in H1299 cells. Dominant negative mutants of caspase-8 and the death receptor adapter protein FADD/MORT1 inhibit E4orf4-induced apoptosis in 293T cells, suggesting that E4orf4 activates the death receptor pathway. Cytochrome c is released into the cytosol in E4orf4-expressing cells, but caspase-9 is not required for induction of apoptosis. Furthermore, E4orf4 induces accumulation of reactive oxygen species (ROS) in a caspase-8- and FADD/MORT1-dependent manner, and inhibition of ROS generation by 4,5-dihydroxy-1,3-benzene-disulfonic acid (Tiron) inhibits E4orf4-induced apoptosis. Thus, our results demonstrate that E4orf4 engages the death receptor pathway to generate at least part of the molecular events required for E4orf4-induced apoptosis.

* Corresponding author. Mailing address: The Gonda Center of Molecular Microbiology, The Bruce Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel. Phone: 972-4-829-5257. Fax: 972-4-829-5225. E-mail: tamark{at}tx.technion.ac.il.

dagger Present address: Molecular, Cellular and Developmental Biology Department, University of California, Santa Barbara, CA 93106.

Journal of Virology, January 2001, p. 789-798, Vol. 75, No. 2
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.2.789-798.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Landry, M.-C., Sicotte, A., Champagne, C., Lavoie, J. N. (2009). Regulation of Cell Death by Recycling Endosomes and Golgi Membrane Dynamics via a Pathway Involving Src-family kinases, Cdc42 and Rab11a. Mol. Biol. Cell 20: 4091-4106 [Abstract] [Full Text]  
  • Li, S., Brignole, C., Marcellus, R., Thirlwell, S., Binda, O., McQuoid, M. J., Ashby, D., Chan, H., Zhang, Z., Miron, M.-J., Pallas, D. C., Branton, P. E. (2009). The Adenovirus E4orf4 Protein Induces G2/M Arrest and Cell Death by Blocking Protein Phosphatase 2A Activity Regulated by the B55 Subunit. J. Virol. 83: 8340-8352 [Abstract] [Full Text]  
  • Miron, M.-J., Blanchette, P., Groitl, P., Dallaire, F., Teodoro, J. G., Li, S., Dobner, T., Branton, P. E. (2009). Localization and Importance of the Adenovirus E4orf4 Protein during Lytic Infection. J. Virol. 83: 1689-1699 [Abstract] [Full Text]  
  • Smadja-Lamere, N., Boulanger, M.-C., Champagne, C., Branton, P. E., Lavoie, J. N. (2008). JNK-mediated Phosphorylation of Paxillin in Adhesion Assembly and Tension-induced Cell Death by the Adenovirus Death Factor E4orf4. J. Biol. Chem. 283: 34352-34364 [Abstract] [Full Text]  
  • Li, Y., Wei, H., Hsieh, T.-C., Pallas, D. C. (2008). Cdc55p-Mediated E4orf4 Growth Inhibition in Saccharomyces cerevisiae Is Mediated Only in Part via the Catalytic Subunit of Protein Phosphatase 2A. J. Virol. 82: 3612-3623 [Abstract] [Full Text]  
  • Robert, A., Smadja-Lamere, N., Landry, M.-C., Champagne, C., Petrie, R., Lamarche-Vane, N., Hosoya, H., Lavoie, J. N. (2006). Adenovirus E4orf4 Hijacks Rho GTPase-dependent Actin Dynamics to Kill Cells: A Role for Endosome-associated Actin Assembly. Mol. Biol. Cell 17: 3329-3344 [Abstract] [Full Text]  
  • Guergnon, J., Dessauge, F., Dominguez, V., Viallet, J., Bonnefoy, S., Yuste, V. J., Mercereau-Puijalon, O., Cayla, X., Rebollo, A., Susin, S. A., Bost, P.-E., Garcia, A. (2006). Use of Penetrating Peptides Interacting with PP1/PP2A Proteins As a General Approach for a Drug Phosphatase Technology. Mol. Pharmacol. 69: 1115-1124 [Abstract] [Full Text]  
  • Maoz, T., Koren, R., Ben-Ari, I., Kleinberger, T. (2005). YND1 Interacts with CDC55 and Is a Novel Mediator of E4orf4-induced Toxicity. J. Biol. Chem. 280: 41270-41277 [Abstract] [Full Text]  
  • Champagne, C., Landry, M.-C., Gingras, M.-C., Lavoie, J. N. (2004). Activation of Adenovirus Type 2 Early Region 4 ORF4 Cytoplasmic Death Function by Direct Binding to Src Kinase Domain. J. Biol. Chem. 279: 25905-25915 [Abstract] [Full Text]  
  • Robert, A., Miron, M.-J., Champagne, C., Gingras, M.-C., Branton, P. E., Lavoie, J. N. (2002). Distinct cell death pathways triggered by the adenovirus early region 4 ORF 4 protein. JCB 158: 519-528 [Abstract] [Full Text]  
  • Hay, S., Kannourakis, G. (2002). A time to kill: viral manipulation of the cell death program. J. Gen. Virol. 83: 1547-1564 [Abstract] [Full Text]  
  • Afifi, R., Sharf, R., Shtrichman, R., Kleinberger, T. (2001). Selection of Apoptosis-Deficient Adenovirus E4orf4 Mutants in Saccharomyces cerevisiae. J. Virol. 75: 4444-4447 [Abstract] [Full Text]  
  • Kornitzer, D., Sharf, R., Kleinberger, T. (2001). Adenovirus E4orf4 protein induces PP2A-dependent growth arrest in Saccharomyces cerevisiae and interacts with the anaphase-promoting complex/cyclosome. JCB 154: 331-344 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»