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 Tang, J.
Right arrow Articles by Foreman, K. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tang, J.
Right arrow Articles by Foreman, K. E.

 Previous Article  |  Next Article 

Journal of Virology, May 2003, p. 5975-5984, Vol. 77, No. 10
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.10.5975-5984.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Induces Expression of the Helix-Loop-Helix Protein Id-1 in Human Endothelial Cells

Jun Tang,1 Gabriel M. Gordon,1 Maike G. Müller,2 Madhu Dahiya,3 and Kimberly E. Foreman1,2*

Department of Pathology and Skin Cancer Research Program, Cardinal Bernardin Cancer Center,1 Department of Microbiology and Immunology, Loyola University Medical Center, Maywood, Illinois 60153,2 Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 022153

Received 3 October 2002/ Accepted 20 February 2003

Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) (also known as human herpesvirus 8) is a gamma-2 herpesvirus believed to be the etiologic agent responsible for KS. The pathogenesis of this potentially life-threatening neoplasm is complex and unclear, and it is currently unknown how KSHV causes KS. Id (named for inhibitor of DNA binding or inhibitor of differentiation) proteins were identified in 1990 and found to be naturally occurring dominant-negative inhibitors of basic helix-loop-helix transcription factors. Id-1, the most well-studied member of this family, has since been shown to play a key role in several biological systems including cellular differentiation, cell cycle regulation, and tumorigenesis. In this report, we demonstrate that Id-1 is expressed at high levels in KS tumor cells both in vitro and in vivo but is expressed at relatively modest levels in endothelial cells (ECs), the likely precursor of the KS tumor cell. Infection of precursor cells with KSHV may be responsible for this enhanced expression, as KSHV infection induced Id-1 27-fold in ECs under our experimental conditions. Furthermore, we demonstrate that the KSHV-encoded latency-associated nuclear antigen (LANA) protein appears to be involved. Expression of LANA in ECs resulted in Id-1 induction that was almost identical to the induction seen with KSHV-infected ECs. These results demonstrate the expression of Id-1 in KS tumor cells and indicate the KSHV LANA protein may be, at least in part, responsible. This may be an important mechanism by which KSHV allows KS tumor cells to escape normal cell cycle regulation and enhances their proliferation.

* Corresponding author. Mailing address: Department of Pathology, Skin Cancer Research Laboratories, Cardinal Bernardin Cancer Center, Room 302, Loyola University Medical Center, 2160 S. First Ave., Maywood, IL 60153-5385. Phone: (708) 327-3320. Fax: (708) 327-3158. E-mail: KFOREMA{at}LUMC.EDU.

Journal of Virology, May 2003, p. 5975-5984, Vol. 77, No. 10
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.10.5975-5984.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lu, J., Verma, S. C., Murakami, M., Cai, Q., Kumar, P., Xiao, B., Robertson, E. S. (2009). Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus (KSHV) Upregulates Survivin Expression in KSHV-Associated B-Lymphoma Cells and Contributes to Their Proliferation. J. Virol. 83: 7129-7141 [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]  
  • Liu, J., Martin, H. J., Liao, G., Hayward, S. D. (2007). The Kaposi's Sarcoma-Associated Herpesvirus LANA Protein Stabilizes and Activates c-Myc. J. Virol. 81: 10451-10459 [Abstract] [Full Text]  
  • Liu, J., Martin, H., Shamay, M., Woodard, C., Tang, Q.-Q., Hayward, S. D. (2007). Kaposi's Sarcoma-Associated Herpesvirus LANA Protein Downregulates Nuclear Glycogen Synthase Kinase 3 Activity and Consequently Blocks Differentiation. J. Virol. 81: 4722-4731 [Abstract] [Full Text]  
  • Grossmann, C., Podgrabinska, S., Skobe, M., Ganem, D. (2006). Activation of NF-{kappa}B by the Latent vFLIP Gene of Kaposi's Sarcoma-Associated Herpesvirus Is Required for the Spindle Shape of Virus-Infected Endothelial Cells and Contributes to Their Proinflammatory Phenotype. J. Virol. 80: 7179-7185 [Abstract] [Full Text]  
  • Fujimuro, M., Liu, J., Zhu, J., Yokosawa, H., Hayward, S. D. (2005). Regulation of the Interaction between Glycogen Synthase Kinase 3 and the Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen. J. Virol. 79: 10429-10441 [Abstract] [Full Text]  
  • Tang, J., Qi, X., Mercola, D., Han, J., Chen, G. (2005). Essential Role of p38{gamma} in K-Ras Transformation Independent of Phosphorylation. J. Biol. Chem. 280: 23910-23917 [Abstract] [Full Text]  
  • Ye, F.-C., Zhou, F.-C., Yoo, S. M., Xie, J.-P., Browning, P. J., Gao, S.-J. (2004). Disruption of Kaposi's Sarcoma-Associated Herpesvirus Latent Nuclear Antigen Leads to Abortive Episome Persistence. J. Virol. 78: 11121-11129 [Abstract] [Full Text]  
  • Qi, X., Tang, J., Pramanik, R., Schultz, R. M., Shirasawa, S., Sasazuki, T., Han, J., Chen, G. (2004). p38 MAPK Activation Selectively Induces Cell Death in K-ras-mutated Human Colon Cancer Cells through Regulation of Vitamin D Receptor. J. Biol. Chem. 279: 22138-22144 [Abstract] [Full Text]  
  • Pan, H.-Y., Zhang, Y.-J., Wang, X.-P., Deng, J.-H., Zhou, F.-C., Gao, S.-J. (2003). Identification of a Novel Cellular Transcriptional Repressor Interacting with the Latent Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus. J. Virol. 77: 9758-9768 [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»