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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,, Michael A. D'silva,^1,, Petric Kuballa,^1, Karin Butz,² Felix Hoppe-Seyler,² and Martin Scheffner^1*

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.

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

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

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

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