A MUTATIONAL ANALYSIS OF THE AMINO-TERMINAL DOMAIN OF THE HUMAN PAPILLOMAVIRUS TYPE-16 E7 ONCOPROTEIN

The human papillomavirus type 16 (HPV-16) E7 oncoprotein shares struct ural and functional similarity with the adenovirus (Ad) E1A protein an d the SV40 large tumor antigen (TAg), Like these other DNA tumor virus oncoproteins, HPV-16 E7 interacts with the ''pocket proteins,'' a fam ily of host cellular proteins that include the retinoblastoma tumor su ppressor protein and can cooperate with the ras oncogene to transform primary rodent cells. Mutational analyses have indicated that amino ac id sequences outside of the pRB binding region are also important for the cellular transformation property oi HPV-16 E7. These sequences inc lude an amino terminal domain of the E7 protein that is similar to a p ortion of conserved region 1 of Ad E1A. In this study it is shown that the homologous amino acid sequences in Ad E1A and SV40 TAg are functi onally interchangeable with the amino terminal HPV-16 E7 domain in tra nsformation assays. Deletion analysis across the amino terminus of HPV -16 E7 indicated that the overall integrity of the entire CR1 homology domain is important for the biological activity oi the HPV E7 oncopro tein. (C) 1994 Academic Press, Inc.