Repression of the integrated papillomavirus E6/E7 promoter is required forgrowth suppression of cervical cancer cells

The human papillomavirus (HPV) E2 protein is an important regulator of vira l E6 and E7 gene expression. E2 can repress the viral promoter for E6 and E 7 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 ha s been well documented, the specific mechanism by which E2 affects cellular proliferation has not yet been elucidated. Here, we show that bovine papil lomavirus (BPV) E2-induced growth arrest of HeLa cells requires the repress ion 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. W e demonstrate that expression of HPV16 E6 and E7 from a heterologous promot er that is not regulated by E2 rescues HeLa cells from E2-mediated growth a rrest. Our data indicate that the pathway of E2-mediated growth arrest of H eLa cells requires repression of E6 and E7 expression through an activity s pecified by the transactivation domain of E2TA.