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 McPhillips, M. G.
Right arrow Articles by McBride, A. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McPhillips, M. G.
Right arrow Articles by McBride, A. A.

 Previous Article  |  Next Article 

Journal of Virology, October 2006, p. 9530-9543, Vol. 80, No. 19
0022-538X/06/$08.00+0     doi:10.1128/JVI.01105-06

Brd4 Is Required for E2-Mediated Transcriptional Activation but Not Genome Partitioning of All Papillomaviruses{dagger}

M. G. McPhillips, J. G. Oliveira, J. E. Spindler, R. Mitra, and A. A. McBride*

Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland

Received 30 May 2006/ Accepted 20 July 2006

Bromodomain protein 4 (Brd4) has been identified as the cellular binding target through which the E2 protein of bovine papillomavirus type 1 links the viral genome to mitotic chromosomes. This tethering ensures retention and efficient partitioning of genomes to daughter cells following cell division. E2 is also a regulator of viral gene expression and a replication factor, in association with the viral E1 protein. In this study, we show that E2 proteins from a wide range of papillomaviruses interact with Brd4, albeit with variations in efficiency. Moreover, disruption of the E2-Brd4 interaction abrogates the transactivation function of E2, indicating that Brd4 is required for E2-mediated transactivation of all papillomaviruses. However, the interaction of E2 and Brd4 is not required for genome partitioning of all papillomaviruses since a number of papillomavirus E2 proteins associate with mitotic chromosomes independently of Brd4 binding. Furthermore, mutations in E2 that disrupt the interaction with Brd4 do not affect the ability of these E2s to associate with chromosomes. Thus, while all papillomaviruses attach their genomes to cellular chromosomes to facilitate genome segregation, they target different cellular binding partners. In summary, the E2 proteins from many papillomaviruses, including the clinically important alpha genus human papillomaviruses, interact with Brd4 to mediate transcriptional activation function but not all depend on this interaction to efficiently associate with mitotic chromosomes.

* Corresponding author. Mailing address: Laboratory of Viral Diseases, NIAID, NIH, Building 4, Room 137, 4 Center Dr., MSC 0455, Bethesda, MD 20892-0455. Phone: (301) 496-1370. Fax: (301) 480-1497. E-mail: amcbride{at}nih.gov.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, October 2006, p. 9530-9543, Vol. 80, No. 19
0022-538X/06/$08.00+0     doi:10.1128/JVI.01105-06




This article has been cited by other articles:

  • You, J., Li, Q., Wu, C., Kim, J., Ottinger, M., Howley, P. M. (2009). Regulation of Aurora B Expression by the Bromodomain Protein Brd4. Mol. Cell. Biol. 29: 5094-5103 [Abstract] [Full Text]  
  • Zheng, G., Schweiger, M.-R., Martinez-Noel, G., Zheng, L., Smith, J. A., Harper, J. W., Howley, P. M. (2009). Brd4 Regulation of Papillomavirus Protein E2 Stability. J. Virol. 83: 8683-8692 [Abstract] [Full Text]  
  • Kapasi, A. J., Clark, C. L., Tran, K., Spector, D. H. (2009). Recruitment of cdk9 to the Immediate-Early Viral Transcriptosomes during Human Cytomegalovirus Infection Requires Efficient Binding to Cyclin T1, a Threshold Level of IE2 86, and Active Transcription. J. Virol. 83: 5904-5917 [Abstract] [Full Text]  
  • Feeney, K. M, Parish, J. L (2009). Targeting mitotic chromosomes: a conserved mechanism to ensure viral genome persistence. Proc R Soc B 276: 1535-1544 [Abstract] [Full Text]  
  • Gagnon, D., Joubert, S., Senechal, H., Fradet-Turcotte, A., Torre, S., Archambault, J. (2009). Proteasomal Degradation of the Papillomavirus E2 Protein Is Inhibited by Overexpression of Bromodomain-Containing Protein 4. J. Virol. 83: 4127-4139 [Abstract] [Full Text]  
  • Kelley-Clarke, B., De Leon-Vazquez, E., Slain, K., Barbera, A. J., Kaye, K. M. (2009). Role of Kaposi's Sarcoma-Associated Herpesvirus C-Terminal LANA Chromosome Binding in Episome Persistence. J. Virol. 83: 4326-4337 [Abstract] [Full Text]  
  • Ottinger, M., Pliquet, D., Christalla, T., Frank, R., Stewart, J. P., Schulz, T. F. (2009). The Interaction of the Gammaherpesvirus 68 orf73 Protein with Cellular BET Proteins Affects the Activation of Cell Cycle Promoters. J. Virol. 83: 4423-4434 [Abstract] [Full Text]  
  • Conway, M.J., Meyers, C. (2009). Replication and Assembly of Human Papillomaviruses. JDR 88: 307-317 [Abstract] [Full Text]  
  • Jang, M. K., Kwon, D., McBride, A. A. (2009). Papillomavirus E2 Proteins and the Host Brd4 Protein Associate with Transcriptionally Active Cellular Chromatin. J. Virol. 83: 2592-2600 [Abstract] [Full Text]  
  • Gammoh, N., Gardiol, D., Massimi, P., Banks, L. (2009). The Mdm2 Ubiquitin Ligase Enhances Transcriptional Activity of Human Papillomavirus E2. J. Virol. 83: 1538-1543 [Abstract] [Full Text]  
  • Lee, A-Y., Chiang, C.-M. (2009). Chromatin Adaptor Brd4 Modulates E2 Transcription Activity and Protein Stability. J. Biol. Chem. 284: 2778-2786 [Abstract] [Full Text]  
  • Poddar, A., Reed, S. C., McPhillips, M. G., Spindler, J. E., McBride, A. A. (2009). The Human Papillomavirus Type 8 E2 Tethering Protein Targets the Ribosomal DNA Loci of Host Mitotic Chromosomes. J. Virol. 83: 640-650 [Abstract] [Full Text]  
  • Lin, A., Wang, S., Nguyen, T., Shire, K., Frappier, L. (2008). The EBNA1 Protein of Epstein-Barr Virus Functionally Interacts with Brd4. J. Virol. 82: 12009-12019 [Abstract] [Full Text]  
  • Cardenas-Mora, J., Spindler, J. E., Jang, M. K., McBride, A. A. (2008). Dimerization of the Papillomavirus E2 Protein Is Required for Efficient Mitotic Chromosome Association and Brd4 Binding. J. Virol. 82: 7298-7305 [Abstract] [Full Text]  
  • Hernandez-Ramon, E. E., Burns, J. E., Zhang, W., Walker, H. F., Allen, S., Antson, A. A., Maitland, N. J. (2008). Dimerization of the Human Papillomavirus Type 16 E2 N Terminus Results in DNA Looping within the Upstream Regulatory Region. J. Virol. 82: 4853-4861 [Abstract] [Full Text]  
  • Kapasi, A. J., Spector, D. H. (2008). Inhibition of the Cyclin-Dependent Kinases at the Beginning of Human Cytomegalovirus Infection Specifically Alters the Levels and Localization of the RNA Polymerase II Carboxyl-Terminal Domain Kinases cdk9 and cdk7 at the Viral Transcriptosome. J. Virol. 82: 394-407 [Abstract] [Full Text]  
  • Schweiger, M.-R., Ottinger, M., You, J., Howley, P. M. (2007). Brd4-Independent Transcriptional Repression Function of the Papillomavirus E2 Proteins. J. Virol. 81: 9612-9622 [Abstract] [Full Text]  
  • Bisgrove, D. A., Mahmoudi, T., Henklein, P., Verdin, E. (2007). Conserved P-TEFb-interacting domain of BRD4 inhibits HIV transcription. Proc. Natl. Acad. Sci. USA 104: 13690-13695 [Abstract] [Full Text]  
  • Wu, S.-Y., Chiang, C.-M. (2007). The Double Bromodomain-containing Chromatin Adaptor Brd4 and Transcriptional Regulation. J. Biol. Chem. 282: 13141-13145 [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»