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 Alam, S.
Right arrow Articles by Meyers, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Alam, S.
Right arrow Articles by Meyers, C.

 Previous Article  |  Next Article 

Journal of Virology, May 2006, p. 4927-4939, Vol. 80, No. 10
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.10.4927-4939.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Adeno-Associated Virus Type 2 Increases Proteosome-Dependent Degradation of p21WAF1 in a Human Papillomavirus Type 31b-Positive Cervical Carcinoma Line

Samina Alam, Ellora Sen,{dagger} Heidi Brashear, and Craig Meyers*

Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033

Received 12 September 2005/ Accepted 21 February 2006

Adeno-associated virus type 2 (AAV2) seropositivity is negatively correlated with the development of human papillomavirus (HPV)-associated cervical cancer. We have begun analysis of the molecular mechanisms underlying AAV2-mediated oncosuppression through cell cycle regulation in HPV-infected keratinocytes isolated from a low-grade cervical lesion. AAV2 superinfection of HPV type 31b (HPV31b)-positive cells at early times postinfection resulted in degradation of the cyclin-dependent kinase (CDK) inhibitor p21WAF1 protein in a proteosome-dependent manner. Downstream consequences of lowering p21WAF1 levels included a proportional loss of cyclin E/CDK2 complexes bound to p21WAF1. The loss of stable p21WAF1/cyclin E/CDK2 complexes coincided with an increase in CDK2-associated kinase activity and cyclin E levels. Both events have the potential to enhance the G1/S transition point mediated by active cyclin E/CDK2 complexes. Concurrently, cyclin A and E2F levels were decreased, conditions reminiscent of delayed entrance into the S phase of the cell cycle. On the other hand, infection of primary human foreskin keratinocytes with AAV2 resulted in upregulation of p21WAF1 protein levels, reminiscent of a block in G1 phase progression. We propose that by downregulating p21WAF1, AAV2 initiates cell cycle activities leading to enhanced G1/S phase-like conditions which may be favorable for AAV2-specific functions and may lead to downstream interference with HPV-associated cervical cancer progression.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA 17033. Phone: (717) 531-6240. Fax: (717) 531-4600. E-mail: cmm10{at}psu.edu.

{dagger} Present address: National Brain Research Centre, Manesar 122 050, Haryana, India.

Journal of Virology, May 2006, p. 4927-4939, Vol. 80, No. 10
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.10.4927-4939.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Alam, S., Conway, M. J., Chen, H.-S., Meyers, C. (2008). The Cigarette Smoke Carcinogen Benzo[a]pyrene Enhances Human Papillomavirus Synthesis. J. Virol. 82: 1053-1058 [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»