Human papillomavirus E7 proteins stimulate proliferation independently of their ability to associate with retinoblastoma protein

Studies on human papillomavirus type 16 have demonstrated that the product of the early gene, E7, plays a key role in the immortalization and malignan t transformation of the host cell. Several of the biological activities of HPV16 E7 are mediated by inactivation of the members of the pocket protein family, pRb, p107 and p130. In this study, we have characterized the in vit ro properties of five E7 proteins from benign and malignant HPV types (10, 32, 48, 54, 77), We show that these E7 proteins associate with pRb and p107 with different efficiencies. All E7s increased the proliferative rate of i mmortalized rodent fibroblasts cultured in 10% calf serum containing medium . This property is completely independent of their ability to associate wit h the pocket proteins. Furthermore, all E7s, except HPV10 E7, stimulate G1/ S progression and activated the cyclin E and cyclin A promoter in the absen ce of growth factors, This activity also does not correlate with the E7-eff iciency of binding the pocket proteins. Together these data provide evidenc e that different E7s alter the regulation of the cell cycle by diverse mech anism(s). Finally, this comparative analysis of the different E7 proteins d emonstrates that the oncogenicity of a HPV type is not determined by the ab ility of E7 to associate with the pocket proteins.