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 Baxter, M. K.
Right arrow Articles by McBride, A. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Baxter, M. K.
Right arrow Articles by McBride, A. A.

 Previous Article  |  Next Article 

Journal of Virology, April 2005, p. 4806-4818, Vol. 79, No. 8
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.8.4806-4818.2005

The Mitotic Chromosome Binding Activity of the Papillomavirus E2 Protein Correlates with Interaction with the Cellular Chromosomal Protein, Brd4

Michael K. Baxter,1 Maria G. McPhillips,1 Keiko Ozato,2 and Alison A. McBride1*

Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases,1 Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland2

Received 17 June 2004/ Accepted 24 November 2004

The papillomavirus transcriptional activator, E2, is involved in key functions of the viral life cycle. These include transcriptional regulation, viral DNA replication, and viral genome segregation. The transactivation domain of E2 is required for each of these functions. To identify the regions of the domain that mediate binding to mitotic chromosomes, a panel of mutations has been generated and their effect on various E2 functions has been analyzed. A structural model of the bovine papillomavirus type 1 (BPV1) E2 transactivation domain was generated based on its homology with the solved structure of the human papillomavirus type 16 (HPV16) domain. This model was used to identify distinct surfaces of the domain to be targeted by point mutation to further delineate the functional region of the transactivation domain responsible for mitotic chromosome association. The mutated E2 proteins were assessed for mitotic chromosome binding and, in addition, transcriptional activation and transcriptional repression activities. Mutation of amino acids R37 and I73, which are located on a surface of the domain that in HPV16 E2 is reported to mediate self-interaction, completely eliminated mitotic chromosome binding. Mitotic chromosome binding activity was found to correlate well with the ability to interact with the cellular chromosomal associated factor Brd4, which has recently been proposed to mediate the association between BPV1 E2 and mitotic chromosomes.

* Corresponding author: 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.

Journal of Virology, April 2005, p. 4806-4818, Vol. 79, No. 8
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.8.4806-4818.2005




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]  
  • 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]  
  • 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]  
  • Mochizuki, K., Nishiyama, A., Jang, M. K., Dey, A., Ghosh, A., Tamura, T., Natsume, H., Yao, H., Ozato, K. (2008). The Bromodomain Protein Brd4 Stimulates G1 Gene Transcription and Promotes Progression to S Phase. J. Biol. Chem. 283: 9040-9048 [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]  
  • Donaldson, M. M., Boner, W., Morgan, I. M. (2007). TopBP1 Regulates Human Papillomavirus Type 16 E2 Interaction with Chromatin. J. Virol. 81: 4338-4342 [Abstract] [Full Text]  
  • Kurg, R., Tekkel, H., Abroi, A., Ustav, M. (2006). Characterization of the Functional Activities of the Bovine Papillomavirus Type 1 E2 Protein Single-Chain Heterodimers. J. Virol. 80: 11218-11225 [Abstract] [Full Text]  
  • McPhillips, M. G., Oliveira, J. G., Spindler, J. E., Mitra, R., McBride, A. A. (2006). Brd4 Is Required for E2-Mediated Transcriptional Activation but Not Genome Partitioning of All Papillomaviruses. J. Virol. 80: 9530-9543 [Abstract] [Full Text]  
  • Schweiger, M.-R., You, J., Howley, P. M. (2006). Bromodomain Protein 4 Mediates the Papillomavirus E2 Transcriptional Activation Function. J. Virol. 80: 4276-4285 [Abstract] [Full Text]  
  • Dao, L. D., Duffy, A., Van Tine, B. A., Wu, S.-Y., Chiang, C.-M., Broker, T. R., Chow, L. T. (2006). Dynamic Localization of the Human Papillomavirus Type 11 Origin Binding Protein E2 through Mitosis While in Association with the Spindle Apparatus.. J. Virol. 80: 4792-4800 [Abstract] [Full Text]  
  • Ilves, I., Maemets, K., Silla, T., Janikson, K., Ustav, M. (2006). Brd4 is involved in multiple processes of the bovine papillomavirus type 1 life cycle.. J. Virol. 80: 3660-3665 [Abstract] [Full Text]  
  • Oliveira, J. G., Colf, L. A., McBride, A. A. (2006). Variations in the association of papillomavirus E2 proteins with mitotic chromosomes. Proc. Natl. Acad. Sci. USA 103: 1047-1052 [Abstract] [Full Text]  
  • Silla, T., Haal, I., Geimanen, J., Janikson, K., Abroi, A., Ustav, E., Ustav, M. (2005). Episomal Maintenance of Plasmids with Hybrid Origins in Mouse Cells. J. Virol. 79: 15277-15288 [Abstract] [Full Text]  
  • You, J., Schweiger, M.-R., Howley, P. M. (2005). Inhibition of E2 Binding to Brd4 Enhances Viral Genome Loss and Phenotypic Reversion of Bovine Papillomavirus-Transformed Cells. J. Virol. 79: 14956-14961 [Abstract] [Full Text]  
  • Viejo-Borbolla, A., Ottinger, M., Bruning, E., Burger, A., Konig, R., Kati, E., Sheldon, J. A., Schulz, T. F. (2005). Brd2/RING3 Interacts with a Chromatin-Binding Domain in the Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen 1 (LANA-1) That Is Required for Multiple Functions of LANA-1. J. Virol. 79: 13618-13629 [Abstract] [Full Text]  
  • Kurg, R., Sild, K., Ilves, A., Sepp, M., Ustav, M. (2005). Association of Bovine Papillomavirus E2 Protein with Nuclear Structures In Vivo. J. Virol. 79: 10528-10539 [Abstract] [Full Text]  
  • McPhillips, M. G., Ozato, K., McBride, A. A. (2005). Interaction of Bovine Papillomavirus E2 Protein with Brd4 Stabilizes Its Association with Chromatin. J. Virol. 79: 8920-8932 [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»