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Journal of Virology, March 2000, p. 2679-2686, Vol. 74, No. 6
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Repression of the Integrated Papillomavirus E6/E7
Promoter Is Required for Growth Suppression of Cervical Cancer
Cells
Delicia A.
Francis,
Susanne
I.
Schmid, and
Peter M.
Howley*
Department of Pathology, Harvard Medical
School, Boston, Massachusetts 02115
Received 2 November 1999/Accepted 16 December 1999
The human papillomavirus (HPV) E2 protein is an important regulator
of viral E6 and E7 gene expression. E2 can repress the viral promoter
for E6 and E7 expression as well as block progression of the cell cycle
in cancer cells harboring the DNA of "high-risk" HPV types.
Although the phenomenon of E2-mediated growth arrest of HeLa cells and
other HPV-positive cancer cells has been well documented, the specific
mechanism by which E2 affects cellular proliferation has not yet been
elucidated. Here, we show that bovine papillomavirus (BPV) E2-induced
growth arrest of HeLa cells requires the repression of the E6 and E7
promoter. This repression is specific for E2TA and not E2TR, a BPV E2
variant that lacks the N-terminal transactivation domain. We
demonstrate that expression of HPV16 E6 and E7 from a heterologous
promoter that is not regulated by E2 rescues HeLa cells from
E2-mediated growth arrest. Our data indicate that the pathway of
E2-mediated growth arrest of HeLa cells requires repression of E6 and
E7 expression through an activity specified by the transactivation
domain of E2TA.
*
Corresponding author. Mailing address: Department of
Pathology, Harvard Medical School, 200 Longwood Ave., Boston, MA 02115. Phone: (617) 432-2884. Fax: (617) 432-2882. E-mail:
peter_howley{at}hms.harvard.edu.
Journal of Virology, March 2000, p. 2679-2686, Vol. 74, No. 6
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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