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 structural and functional similarity with the adenovirus (Ad) E1A protein and the SV40 large tumor antigen (TAg). Like these other DNA tumor virus oncoproteins, HPV-16 E7 interacts with the "pocket proteins," a family of host cellular proteins that include the retinoblastoma tumor suppressor protein and can cooperate with the ras oncogene to transform primary rodent cells. Mutational analyses have indicated that amino acid sequences outside of the pRB binding region are also important for the cellular transformation property of HPV-16 E7. These sequences include an amino terminal domain of the E7 protein that is similar to a portion 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 functionally interchangeable with the amino terminal HPV-16 E7 domain in transformation 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 of the HPV E7 oncoprotein.
Laboratory of Tumor Virus Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
J L
JL
Brokaw
C L
CL
Yee
K
K
Münger
D017500:Adenovirus E1A Proteins / Q000737:chemistry; D000595:Amino Acid Sequence; D000952:Antigens, Polyomavirus Transforming / Q000737:chemistry; D002460:Cell Line; D002472:Cell Transformation, Viral / Q000502:physiology; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D027383:Papillomaviridae / Q000737:chemistry* / Q000235:genetics; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins / Q000737:chemistry
D017500:Adenovirus E1A Proteins; D000952:Antigens, Polyomavirus Transforming; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; C059731:oncogene protein E7, Human papillomavirus type 16