Mechanisms of human papillomavirus E2-mediated repression of viral oncogene expression and cervical cancer cell growth inhibition

The papillomavirus E2 gene product plays a pivotal role in viral replicatio n. E2 has multiple functions, including (i) transcriptional activation and repression of viral promoters and (ii) the enhancement of viral DNA replica tion. It was previously reported that E2 suppressed the growth of papilloma virus-positive cervical carcinoma cell lines. In the present study, we inve stigated the mechanisms of E2 growth inhibition. We found that the transcri ptional 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 t o the E6/E7 promoter and displacing other cellular transcriptional factors. In this study, we report a requirement for the transcription activation fu nction for the binding of E2 to transcriptionally active templates.