This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by James, M. A. Articles by Klingelhutz, A. J. Search for Related Content PubMed PubMed Citation Articles by James, M. A. Articles by Klingelhutz, A. J.

 Previous Article  |  Next Article 

Journal of Virology, June 2006, p. 5301-5307, Vol. 80, No. 11
0022-538X/06/$08.00+0     doi:10.1128/JVI.01942-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Human Papillomavirus Type 16 E6 Activates NF-B, Induces cIAP-2 Expression, and Protects against Apoptosis in a PDZ Binding Motif-Dependent Manner

Department of Microbiology and Holden Cancer Center, University of Iowa, Iowa City, Iowa,¹ Department of Otolaryngology, University of Iowa Health Care, Iowa City, Iowa²

Received 13 September 2005/ Accepted 13 March 2006

Infection with human papillomavirus (HPV) is a critical factor in the pathogenesis of most cervical cancers and some aerodigestive cancers. The HPV E6 oncoprotein from high-risk HPV types contributes to the immortalization and transformation of cells by multiple mechanisms, including degradation of p53, transcriptional activation of human telomerase reverse transcriptase (hTERT), and degradation of several proteins containing PDZ domains. The ability of E6 to bind PDZ domain-containing proteins is independent of p53 degradation or hTERT activation but does correlate with oncogenic potential (R. A. Watson, M. Thomas, L. Banks, and S. Roberts, J. Cell Sci. 116:4925-4934, 2003) and is essential for induction of epithelial hyperplasia in vivo (M. L. Nguyen, M. M. Nguyen, D. Lee, A. E. Griep, and P. F. Lambert, J. Virol. 77:6957-6964, 2003). In this study, we found that HPV type 16 E6 was able to activate NF-B in airway epithelial cells through the induction of nuclear binding activity of p52-containing NF-B complexes in a PDZ binding motif-dependent manner. Transcript accumulation for the NF-B-responsive antiapoptotic gene encoding cIAP-2 and binding of nuclear factors to the proximal NF-B binding site of the cIAP-2 gene promoter are induced by E6 expression. Furthermore, E6 is able to protect cells from TNF-induced apoptosis. All of these E6-dependent phenotypes are dependent on the presence of the PDZ binding motif of E6. Our results imply a role for targeting of PDZ proteins by E6 in NF-B activation and protection from apoptosis in airway epithelial cells.

This article has been cited by other articles:

• Liu, J., Enomoto, S., Lancto, C. A., Abrahamsen, M. S., Rutherford, M. S. (2008). Inhibition of Apoptosis in Cryptosporidium parvum-Infected Intestinal Epithelial Cells Is Dependent on Survivin. Infect. Immun. 76: 3784-3792 [Abstract] [Full Text]  
• Higuchi, M., Tsubata, C., Kondo, R., Yoshida, S., Takahashi, M., Oie, M., Tanaka, Y., Mahieux, R., Matsuoka, M., Fujii, M. (2007). Cooperation of NF-{kappa}B2/p100 Activation and the PDZ Domain Binding Motif Signal in Human T-Cell Leukemia Virus Type 1 (HTLV-1) Tax1 but Not HTLV-2 Tax2 Is Crucial for Interleukin-2-Independent Growth Transformation of a T-Cell Line. J. Virol. 81: 11900-11907 [Abstract] [Full Text]  
• Zhang, Y., Dasgupta, J., Ma, R. Z., Banks, L., Thomas, M., Chen, X. S. (2007). Structures of a Human Papillomavirus (HPV) E6 Polypeptide Bound to MAGUK Proteins: Mechanisms of Targeting Tumor Suppressors by a High-Risk HPV Oncoprotein. J. Virol. 81: 3618-3626 [Abstract] [Full Text]