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Journal of Virology, April 2000, p. 3752-3760, Vol. 74, No. 8
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Mechanisms of Human Papillomavirus E2-Mediated Repression of Viral Oncogene Expression and Cervical Cancer Cell Growth Inhibition

Akiko Nishimura,1 Takeshi Ono,1 Akinori Ishimoto,1 Jennifer J. Dowhanick,2 Margaret A. Frizzell,2 Peter M. Howley,2 and Hiroyuki Sakai1,*

Laboratory of Gene Analysis, Department of Viral Oncology, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan,1 and Department of Pathology, Harvard Medical School, Boston, Massachusetts 021152

Received 11 October 1999/Accepted 11 January 2000

The papillomavirus E2 gene product plays a pivotal role in viral replication. E2 has multiple functions, including (i) transcriptional activation and repression of viral promoters and (ii) the enhancement of viral DNA replication. It was previously reported that E2 suppressed the growth of papillomavirus-positive cervical carcinoma cell lines. In the present study, we investigated the mechanisms of E2 growth inhibition. We found that the transcriptional activation function of E2 is required for inhibition of the growth of HeLa cells as well as for transcriptional repression of the viral E6/E7 promoter. It had been previously postulated that transcriptional repression of the E6/E7 promoter results from E2 binding its cognate sites proximal to the E6/E7 promoter and displacing other cellular transcriptional factors. In this study, we report a requirement for the transcription activation function for the binding of E2 to transcriptionally active templates.

* Corresponding author. Mailing address: Laboratory of Gene Analysis, Department of Viral Oncology, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan. Phone: 81-75-751-4010. Fax: 81-75-751-3995. E-mail: hsakai{at}virus.kyoto-u.ac.jp.

Journal of Virology, April 2000, p. 3752-3760, Vol. 74, No. 8
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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