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 Dahl, J.
Right arrow Articles by Benjamin, T. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dahl, J.
Right arrow Articles by Benjamin, T. L.

 Previous Article  |  Next Article 

J Virol, April 1998, p. 3221-3226, Vol. 72, No. 4
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Evidence of a Role for Phosphatidylinositol 3-Kinase Activation in the Blocking of Apoptosis by Polyomavirus Middle T Antigen

Jean Dahl,1 Annmarie Jurczak,1 Linda A. Cheng,1 David C. Baker,2 and Thomas L. Benjamin1,*

Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115,1 and Department of Chemistry, The University of Tennessee, Knoxville, Tennessee 379962

Received 29 August 1997/Accepted 12 December 1997

A polyomavirus mutant (315YF) blocked in binding phosphatidylinositol 3-kinase (PI 3-kinase) has previously been shown to be partially deficient in transformation and to induce fewer tumors and with a significant delay compared to wild-type virus. The role of polyomavirus middle T antigen-activated PI 3-kinase in apoptosis was investigated as a possible cause of this behavior. When grown in medium containing 1D-3-deoxy-3-fluoro-myo-inositol to block formation of 3'-phosphorylated phosphatidylinositols, F111 rat fibroblasts transformed by wild-type polyomavirus (PyF), but not normal F111 cells, showed a marked loss of viability with evidence of apoptosis. Similarly, treatment with wortmannin, an inhibitor of PI 3-kinase, stimulated apoptosis in PyF cells but not in normal cells. Activation of Akt, a serine/threonine kinase whose activity has been correlated with regulation of apoptosis, was roughly twofold higher in F111 cells transformed by either wild-type virus or mutant 250YS blocked in binding Shc compared to cells transformed by mutant 315YF. In the same cells, levels of apoptosis were inversely correlated with Akt activity. Apoptosis induced by serum withdrawal in Rat-1 cells expressing a temperature-sensitive p53 was shown to be at least partially p53 independent. Expression of either wild-type or 250YS middle T antigen inhibited apoptosis in serum-starved Rat-1 cells at both permissive and restrictive temperatures for p53. Mutant 315YF middle T antigen was partially defective for inhibition of apoptosis in these cells. The results indicate that unlike other DNA tumor viruses which block apoptosis by inactivation of p53, polyomavirus achieves protection from apoptotic death through a middle T antigen-PI 3-kinase-Akt pathway that is at least partially p53 independent.

* Corresponding author. Mailing address: Department of Pathology, Harvard Medical School, 200 Longwood Ave., D2-230, Boston, MA 02115. Phone: (617) 432-1960. Fax: (617) 277-5291. E-mail: tbenjamin{at}warren.med.harvard.edu.




This article has been cited by other articles:

  • Whalen, K. A., Weber, G. F., Benjamin, T. L., Schaffhausen, B. S. (2008). Polyomavirus Middle T Antigen Induces the Transcription of Osteopontin, a Gene Important for the Migration of Transformed Cells. J. Virol. 82: 4946-4954 [Abstract] [Full Text]  
  • Autret, A., Martin-Latil, S., Brisac, C., Mousson, L., Colbere-Garapin, F., Blondel, B. (2008). Early Phosphatidylinositol 3-Kinase/Akt Pathway Activation Limits Poliovirus-Induced JNK-Mediated Cell Death. J. Virol. 82: 3796-3802 [Abstract] [Full Text]  
  • Dahl, J., You, J., Benjamin, T. L. (2005). Induction and Utilization of an ATM Signaling Pathway by Polyomavirus. J. Virol. 79: 13007-13017 [Abstract] [Full Text]  
  • Mannova, P., Beretta, L. (2005). Activation of the N-Ras-PI3K-Akt-mTOR Pathway by Hepatitis C Virus: Control of Cell Survival and Viral Replication. J. Virol. 79: 8742-8749 [Abstract] [Full Text]  
  • Yu, Y., Kudchodkar, S. B., Alwine, J. C. (2005). Effects of Simian Virus 40 Large and Small Tumor Antigens on Mammalian Target of Rapamycin Signaling: Small Tumor Antigen Mediates Hypophosphorylation of eIF4E-Binding Protein 1 Late in Infection. J. Virol. 79: 6882-6889 [Abstract] [Full Text]  
  • Kudchodkar, S. B., Yu, Y., Maguire, T. G., Alwine, J. C. (2004). Human Cytomegalovirus Infection Induces Rapamycin-Insensitive Phosphorylation of Downstream Effectors of mTOR Kinase. J. Virol. 78: 11030-11039 [Abstract] [Full Text]  
  • Cooray, S. (2004). The pivotal role of phosphatidylinositol 3-kinase-Akt signal transduction in virus survival. J. Gen. Virol. 85: 1065-1076 [Abstract] [Full Text]  
  • Fukuda, M., Longnecker, R. (2004). Latent Membrane Protein 2A Inhibits Transforming Growth Factor-{beta}1-Induced Apoptosis through the Phosphatidylinositol 3-Kinase/Akt Pathway. J. Virol. 78: 1697-1705 [Abstract] [Full Text]  
  • Dawson, C. W., Tramountanis, G., Eliopoulos, A. G., Young, L. S. (2003). Epstein-Barr Virus Latent Membrane Protein 1 (LMP1) Activates the Phosphatidylinositol 3-Kinase/Akt Pathway to Promote Cell Survival and Induce Actin Filament Remodeling. J. Biol. Chem. 278: 3694-3704 [Abstract] [Full Text]  
  • He, Y., Nakao, H., Tan, S.-L., Polyak, S. J., Neddermann, P., Vijaysri, S., Jacobs, B. L., Katze, M. G. (2002). Subversion of Cell Signaling Pathways by Hepatitis C Virus Nonstructural 5A Protein via Interaction with Grb2 and P85 Phosphatidylinositol 3-Kinase. J. Virol. 76: 9207-9217 [Abstract] [Full Text]  
  • Dey, D., Dahl, J., Cho, S., Benjamin, T. L. (2002). Induction and Bypass of p53 during Productive Infection by Polyomavirus. J. Virol. 76: 9526-9532 [Abstract] [Full Text]  
  • Zhang, B., Spandau, D. F., Roman, A. (2002). E5 Protein of Human Papillomavirus Type 16 Protects Human Foreskin Keratinocytes from UV B-Irradiation-Induced Apoptosis. J. Virol. 76: 220-231 [Abstract] [Full Text]  
  • Gottlieb, K. A., Villarreal, L. P. (2001). Natural Biology of Polyomavirus Middle T Antigen. Microbiol. Mol. Biol. Rev. 65: 288-318 [Abstract] [Full Text]  
  • Sanjuan, N., Porrás, A., Otero, J., Perazzo, S. (2001). Expression of Major Capsid Protein VP-1 in the Absence of Viral Particles in Thymomas Induced by Murine Polyomavirus. J. Virol. 75: 2891-2899 [Abstract] [Full Text]  
  • Montaner, S., Sodhi, A., Pece, S., Mesri, E. A., Gutkind, J. S. (2001). The Kaposi's Sarcoma-associated Herpesvirus G Protein-coupled Receptor Promotes Endothelial Cell Survival through the Activation of Akt/Protein Kinase B. Cancer Res. 61: 2641-2648 [Abstract] [Full Text]  
  • Dey, D. C., Bronson, R. P., Dahl, J., Carroll, J. P., Benjamin, T. L. (2000). Accelerated Development of Polyoma Tumors and Embryonic Lethality: Different Effects of p53 Loss on Related Mouse Backgrounds. Cell Growth Differ. 11: 231-237 [Abstract] [Full Text]  
  • Qian, W., Wiman, K. G. (2000). Polyoma Virus Middle T and Small t Antigens Cooperate to Antagonize p53-induced Cell Cycle Arrest and Apoptosis. Cell Growth Differ. 11: 31-39 [Abstract] [Full Text]  
  • Carroll, J. P., Fung, J. S., Bronson, R. T., Razvi, E., Benjamin, T. L. (1999). Radiation-Resistant and Radiation-Sensitive Forms of Host Resistance to Polyomavirus. J. Virol. 73: 1213-1218 [Abstract] [Full Text]  
  • Aoki, M., Batista, O., Bellacosa, A., Tsichlis, P., Vogt, P. K. (1998). The Akt kinase: Molecular determinants of oncogenicity. Proc. Natl. Acad. Sci. USA 95: 14950-14955 [Abstract] [Full Text]  
  • Shih, W.-L., Kuo, M.-L., Chuang, S.-E., Cheng, A.-L., Doong, S.-L. (2000). Hepatitis B Virus X Protein Inhibits Transforming Growth Factor-beta -induced Apoptosis through the Activation of Phosphatidylinositol 3-Kinase Pathway. J. Biol. Chem. 275: 25858-25864 [Abstract] [Full Text]  
  • Lee, Y. I., Kang-Park, S., Do, S.-I., Lee, Y. I. (2001). The Hepatitis B Virus-X Protein Activates a Phosphatidylinositol 3-Kinase-dependent Survival Signaling Cascade. J. Biol. Chem. 276: 16969-16977 [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»