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
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
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 Tyagarajan, S. K.
Right arrow Articles by Frisque, R. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tyagarajan, S. K.
Right arrow Articles by Frisque, R. J.

 Previous Article  |  Next Article 

Journal of Virology, March 2006, p. 2083-2091, Vol. 80, No. 5
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.5.2083-2091.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Stability and Function of JC Virus Large T Antigen and T' Proteins Are Altered by Mutation of Their Phosphorylated Threonine 125 Residues

Shiva K. Tyagarajan and Richard J. Frisque*

Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802

Received 8 September 2005/ Accepted 6 December 2005

JC virus (JCV), a human polyomavirus, exhibits oncogenic activity in rodents and primates. The large tumor antigens (TAgs) of the polyomaviruses play key roles in viral replication and oncogenic transformation. Analyses of JCV TAg phosphorylation mutants indicated that the amino-terminal phosphorylation site at threonine 125 (T125) is critical to TAg replication function. This site is also conserved in the TAg splice variants T'135, T'136, and T'165. By constructing stable cell lines expressing JCV T125A and T125D mutants, we show that mutation of this phosphorylation site to alanine generates an unstable TAg; however, the stability of the three T' proteins is unaffected. JCV T125A mutant proteins bind the retinoblastoma protein (RB) family members p107 and p130 with slightly reduced efficiencies and fail to induce the release of transcriptionally active E2F from RB-E2F complexes. On the other hand, cell lines expressing JCV T125D mutant proteins produce stable TAg and T' proteins which bind p107 and p130 more efficiently than do the wild-type proteins. In addition, T125D mutant proteins efficiently induce the release of E2F from RB-E2F complexes. T125D mutant cell lines, unlike the T125A mutant lines, continue to grow under conditions of low serum concentration and anchorage independence. Finally, both T125A and T125D mutant viruses are replication defective. Phosphorylation of the T125 site is likely mediated by a cyclin-cyclin-dependent kinase, suggesting that JCV TAg and T' protein functions that mediate viral replication and oncogenic transformation events are regulated in a cell cycle-dependent manner.

* Corresponding author. Mailing address: 433 S. Frear Building, The Pennsylvania State University, University Park, PA 16802. Phone: (814) 863-3523. Fax: (814) 865-1285. E-mail: rjf6{at}psu.edu.

Journal of Virology, March 2006, p. 2083-2091, Vol. 80, No. 5
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.5.2083-2091.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • White, M. K., Safak, M., Khalili, K. (2009). Regulation of Gene Expression in Primate Polyomaviruses. J. Virol. 83: 10846-10856 [Abstract] [Full Text]  
  • Manley, K., O'Hara, B. A., Gee, G. V., Simkevich, C. P., Sedivy, J. M., Atwood, W. J. (2006). NFAT4 Is Required for JC Virus Infection of Glial Cells. J. Virol. 80: 12079-12085 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»