Journal article
Human Papillomavirus Type 16 E6 Activates NF-κB, Induces cIAP-2 Expression, and Protects against Apoptosis in a PDZ Binding Motif-Dependent Manner
Journal of virology, Vol.80(11), pp.5301-5307
06/2006
DOI: 10.1128/JVI.01942-05
PMCID: PMC1472131
PMID: 16699010
Abstract
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-κB in airway epithelial cells through the induction of nuclear binding activity of p52-containing NF-κB complexes in a PDZ binding motif-dependent manner. Transcript accumulation for the NF-κB-responsive antiapoptotic gene encoding cIAP-2 and binding of nuclear factors to the proximal NF-κB 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-κB activation and protection from apoptosis in airway epithelial cells.
Details
- Title: Subtitle
- Human Papillomavirus Type 16 E6 Activates NF-κB, Induces cIAP-2 Expression, and Protects against Apoptosis in a PDZ Binding Motif-Dependent Manner
- Creators
- Michael A James - Department of Otolaryngology, University of Iowa Health Care, Iowa City, IowaJohn H Lee - Department of Otolaryngology, University of Iowa Health Care, Iowa City, IowaAloysius J Klingelhutz - Department of Otolaryngology, University of Iowa Health Care, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.80(11), pp.5301-5307
- DOI
- 10.1128/JVI.01942-05
- PMID
- 16699010
- PMCID
- PMC1472131
- NLM abbreviation
- J Virol
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Publisher
- American Society for Microbiology
- Language
- English
- Date published
- 06/2006
- Academic Unit
- Microbiology and Immunology; Radiation Oncology
- Record Identifier
- 9984001204402771
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