CELL CYCLE-DEPENDENT DISRUPTION OF E2F-P107 COMPLEXES BY HUMAN PAPILLOMAVIRUS TYPE-16 E7

The human papillomavirus type 16 (HPV-16) E7 and adenovirus (Ad) E1A o ncoproteins share a common pathway of transformation. They disrupt the cell cycle G(1) phase-specific protein complex containing the E2F tra nscription factor and the regulatory protein Rbl, the retinoblastoma t umour suppressor gene product. In the G(1) and S phases of the cell cy cle, E7 and E1A bind two other cellular complexes containing the Rb1-r elated protein p107 and E2F. Ad E1A disrupts both complexes and releas es active E2F. In contrast, HPV-16 E7, although it efficiently binds b oth E2F-p107 complexes, causes dissociation of the G(1) phase complex only. Using chimeric proteins of HPV-16 E7 and Ad E1A we were able to demonstrate that the ability of E1A to disrupt both G(1) and S phase E 2F-p107 complexes is not due to the higher concentration of Ad E1A in the cell, but is an intrinsic property of the Ad E1A transforming regi on. These data suggest that EIA and E7 may function in cellular transf ormation in similar, but not identical ways.