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Journal of Virology, April 2000, p. 3752-3760, Vol. 74, No. 8
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.
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
*
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.
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