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 Nevels, M.
Right arrow Articles by Dobner, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nevels, M.
Right arrow Articles by Dobner, T.

 Previous Article  |  Next Article 

Journal of Virology, February 1999, p. 1591-1600, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Transforming Potential of the Adenovirus Type 5 E4orf3 Protein

Michael Nevels,1 Birgitt Täuber,1 Elisabeth Kremmer,2 Thilo Spruss,1 Hans Wolf,1 and Thomas Dobner1,*

Institut für Medizinische Mikrobiologie und Hygiene, Universität Regensburg, D-93053 Regensburg,1 and GSF-Institut für Molekulare Immunologie und Hygiene, D-81337 München,2 Germany

Received 18 June 1998/Accepted 5 November 1998

Previous observations that the adenovirus type 5 (Ad5) E4orf6 and E4orf3 gene products have redundant effects in viral lytic infection together with the recent findings that E4orf6 possesses transforming potential prompted us to investigate the effect of E4orf3 expression on the transformation of primary rat cells in combination with adenovirus E1 oncogene products. Our results demonstrate for the first time that E4orf3 can cooperate with adenovirus E1A and E1A plus E1B proteins to transform primary baby rat kidney cells, acting synergistically with E4orf6 in the presence of E1B gene products. Transformed rat cells expressing E4orf3 exhibit morphological alterations, higher growth rates and saturation densities, and increased tumorigenicity compared with transformants expressing E1 proteins only. Consistent with previous results for adenovirus-infected cells, the E4orf3 protein is immunologically restricted to discrete nuclear structures known as PML oncogenic domains (PODs) in transformed rat cells. As opposed to E4orf6, the ability of E4orf3 to promote oncogenic cell growth is probably not linked to a modulation of p53 functions and stability. Instead, our results indicate that the transforming activities of E4orf3 are due to combinatorial effects that involve the binding to the adenovirus 55-kDa E1B protein and the colocalization with PODs independent from interactions with the PML gene product. These data fit well with a model in which the reorganization of PODs may trigger a cascade of processes that cause uncontrolled cell proliferation and neoplastic growth. In sum, our results provide strong evidence for the idea that interactions with PODs by viral proteins are linked to oncogenic transformation.

* Corresponding author. Mailing address: Institut für Medizinische Mikrobiologie und Hygiene, Universität Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg, Germany. Phone: 49-941-944-6475. Fax: 49-941-944-6402. E-mail: Thomas.Dobner{at}klinik.uni-regensburg.de.

Journal of Virology, February 1999, p. 1591-1600, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Dallaire, F., Blanchette, P., Groitl, P., Dobner, T., Branton, P. E. (2009). Identification of Integrin {alpha}3 as a New Substrate of the Adenovirus E4orf6/E1B 55-Kilodalton E3 Ubiquitin Ligase Complex. J. Virol. 83: 5329-5338 [Abstract] [Full Text]  
  • Blackford, A. N., Grand, R. J. A. (2009). Adenovirus E1B 55-Kilodalton Protein: Multiple Roles in Viral Infection and Cell Transformation. J. Virol. 83: 4000-4012 [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]  
  • Leppard, K. N., Emmott, E., Cortese, M. S., Rich, T. (2009). Adenovirus type 5 E4 Orf3 protein targets promyelocytic leukaemia (PML) protein nuclear domains for disruption via a sequence in PML isoform II that is predicted as a protein interaction site by bioinformatic analysis. J. Gen. Virol. 90: 95-104 [Abstract] [Full Text]  
  • Blanchette, P., Kindsmuller, K., Groitl, P., Dallaire, F., Speiseder, T., Branton, P. E., Dobner, T. (2008). Control of mRNA Export by Adenovirus E4orf6 and E1B55K Proteins during Productive Infection Requires E4orf6 Ubiquitin Ligase Activity. J. Virol. 82: 2642-2651 [Abstract] [Full Text]  
  • Yondola, M. A., Hearing, P. (2007). The Adenovirus E4 ORF3 Protein Binds and Reorganizes the TRIM Family Member Transcriptional Intermediary Factor 1 Alpha. J. Virol. 81: 4264-4271 [Abstract] [Full Text]  
  • Sieber, T., Dobner, T. (2007). Adenovirus Type 5 Early Region 1B 156R Protein Promotes Cell Transformation Independently of Repression of p53-Stimulated Transcription. J. Virol. 81: 95-105 [Abstract] [Full Text]  
  • Hoppe, A., Beech, S. J., Dimmock, J., Leppard, K. N. (2006). Interaction of the Adenovirus Type 5 E4 Orf3 Protein with Promyelocytic Leukemia Protein Isoform II Is Required for ND10 Disruption. J. Virol. 80: 3042-3049 [Abstract] [Full Text]  
  • Liu, Y., Shevchenko, A., Shevchenko, A., Berk, A. J. (2005). Adenovirus Exploits the Cellular Aggresome Response To Accelerate Inactivation of the MRN Complex. J. Virol. 79: 14004-14016 [Abstract] [Full Text]  
  • Stracker, T. H., Lee, D. V., Carson, C. T., Araujo, F. D., Ornelles, D. A., Weitzman, M. D. (2005). Serotype-Specific Reorganization of the Mre11 Complex by Adenoviral E4orf3 Proteins. J. Virol. 79: 6664-6673 [Abstract] [Full Text]  
  • Shepard, R. N., Ornelles, D. A. (2004). Diverse Roles for E4orf3 at Late Times of Infection Revealed in an E1B 55-Kilodalton Protein Mutant Background. J. Virol. 78: 9924-9935 [Abstract] [Full Text]  
  • Evans, J. D., Hearing, P. (2003). Distinct Roles of the Adenovirus E4 ORF3 Protein in Viral DNA Replication and Inhibition of Genome Concatenation. J. Virol. 77: 5295-5304 [Abstract] [Full Text]  
  • Lethbridge, K. J., Scott, G. E., Leppard, K. N. (2003). Nuclear matrix localization and SUMO-1 modification of adenovirus type 5 E1b 55K protein are controlled by E4 Orf6 protein. J. Gen. Virol. 84: 259-268 [Abstract] [Full Text]  
  • Oswald, F., Tauber, B., Dobner, T., Bourteele, S., Kostezka, U., Adler, G., Liptay, S., Schmid, R. M. (2001). p300 Acts as a Transcriptional Coactivator for Mammalian Notch-1. Mol. Cell. Biol. 21: 7761-7774 [Abstract] [Full Text]  
  • Endter, C., Kzhyshkowska, J., Stauber, R., Dobner, T. (2001). SUMO-1 modification required for transformation by adenovirus type 5 early region 1B 55-kDa oncoprotein. Proc. Natl. Acad. Sci. USA 10.1073/pnas.191361798v1 [Abstract] [Full Text]  
  • Dosch, T., Horn, F., Schneider, G., Krätzer, F., Dobner, T., Hauber, J., Stauber, R. H. (2001). The Adenovirus Type 5 E1B-55K Oncoprotein Actively Shuttles in Virus-Infected Cells, Whereas Transport of E4orf6 Is Mediated by a CRM1-Independent Mechanism. J. Virol. 75: 5677-5683 [Abstract] [Full Text]  
  • Wienzek, S., Dobbelstein, M. (2001). Viral and Cellular Factors That Target the Promyelocytic Leukemia Oncogenic Domains Strongly Activate a Glucocorticoid-Responsive Promoter. J. Virol. 75: 5391-5397 [Abstract] [Full Text]  
  • Nevels, M., Täuber, B., Spruss, T., Wolf, H., Dobner, T. (2001). "Hit-and-Run" Transformation by Adenovirus Oncogenes. J. Virol. 75: 3089-3094 [Abstract] [Full Text]  
  • Doronin, K., Kuppuswamy, M., Toth, K., Tollefson, A. E., Krajcsi, P., Krougliak, V., Wold, W. S. M. (2001). Tissue-Specific, Tumor-Selective, Replication-Competent Adenovirus Vector for Cancer Gene Therapy. J. Virol. 75: 3314-3324 [Abstract] [Full Text]  
  • Thomas, D. L., Schaack, J., Vogel, H., Javier, R. (2001). Several E4 Region Functions Influence Mammary Tumorigenesis by Human Adenovirus Type 9. J. Virol. 75: 557-568 [Abstract] [Full Text]  
  • Nevels, M., Rubenwolf, S., Spruss, T., Wolf, H., Dobner, T. (2000). Two Distinct Activities Contribute to the Oncogenic Potential of the Adenovirus Type 5 E4orf6 Protein. J. Virol. 74: 5168-5181 [Abstract] [Full Text]  
  • Goodrum, F. D., Ornelles, D. A. (1999). Roles for the E4 orf6, orf3, and E1B 55-Kilodalton Proteins in Cell Cycle-Independent Adenovirus Replication. J. Virol. 73: 7474-7488 [Abstract] [Full Text]  
  • Young, P. J., Day, P. M., Zhou, J., Androphy, E. J., Morris, G. E., Lorson, C. L. (2002). A Direct Interaction between the Survival Motor Neuron Protein and p53 and Its Relationship to Spinal Muscular Atrophy. J. Biol. Chem. 277: 2852-2859 [Abstract] [Full Text]  
  • Endter, C., Kzhyshkowska, J., Stauber, R., Dobner, T. (2001). SUMO-1 modification required for transformation by adenovirus type 5 early region 1B 55-kDa oncoprotein. Proc. Natl. Acad. Sci. USA 98: 11312-11317 [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»