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Journal of Virology, July 2005, p. 9296-9300, Vol. 79, No. 14
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.14.9296-9300.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Growth Suppression Induced by Downregulation of E6-AP Expression in Human Papillomavirus-Positive Cancer Cell Lines Depends on p53

Arnd Hengstermann ,1,{dagger},§ Michael A. D'silva,1,{ddagger},§ Petric Kuballa,1,{ddagger} Karin Butz,2 Felix Hoppe-Seyler,2 and Martin Scheffner1*

Center for Biochemistry, Faculty of Medicine, and Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany,1 Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany2

Received 27 September 2004/ Accepted 31 March 2005

The ubiquitin-protein ligase E6-AP is utilized by the E6 oncoprotein of human papillomaviruses (HPVs) associated with cervical cancer to target the tumor suppressor p53 for degradation. Here, we report that downregulation of E6-AP expression by RNA interference results in both the accumulation of p53 and growth suppression of the HPV-positive cervical cancer cell lines HeLa and SiHa. In addition, HeLa cells, in which p53 expression was suppressed by RNA interference, are significantly less sensitive to the downregulation of E6-AP expression with respect to growth suppression than parental HeLa cells. These data indicate that the anti-growth-suppressive properties of E6-AP in HPV-positive cells depend on its ability to induce p53 degradation.

* Corresponding author. Present address: Department of Biology, University of Konstanz, 78457 Constance, Germany. Phone: 49-7531-885150. Fax: 49-7531-883042. E-mail: martin.scheffner{at}uni-konstanz.de.

{dagger} Present address: Philip Morris Research Laboratories, Fuggerstr. 3, 51149 Cologne, Germany.

§ A.H. and M.A.D. contributed equally to this work.

{ddagger} Present address: Dept. of Biology, University of Konstanz, 78457 Constance, Germany.

Journal of Virology, July 2005, p. 9296-9300, Vol. 79, No. 14
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.14.9296-9300.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kuballa, P., Matentzoglu, K., Scheffner, M. (2007). The Role of the Ubiquitin Ligase E6-AP in Human Papillomavirus E6-mediated Degradation of PDZ Domain-containing Proteins. J. Biol. Chem. 282: 65-71 [Abstract] [Full Text]  
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  • Pauls, E., Senserrich, J., Clotet, B., Este, J. A. (2006). Inhibition of HIV-1 replication by RNA interference of p53 expression. J. Leukoc. Biol. 80: 659-667 [Abstract] [Full Text]  


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