Comparison of the binding of the human papillomavirus type 16 and cottontail rabbit papillomavirus E7 proteins to the retinoblastoma gene product.
Binding of the human papillomavirus type 16 (HPV-16) E7 oncoprotein to the retinoblastoma protein (pRb) is thought to be involved in the cellular transformation mediated by HPV-16. Here we show that the E7 protein of the cottontail rabbit papillomavirus (CRPV) binds to the same C-terminal portion of human pRb as HPV-16 E7, and that both the CRPV and HPV-16 E7 proteins bind specifically through similar domains to rabbit pRb. Furthermore, a single amino acid substitution which reduces the binding of HPV-16 E7 to human pRb also abolishes binding of CRPV E7 to both human and rabbit pRb. The biochemical similarities observed between the HPV-16 and CRPV E7 proteins suggest that they are functionally conserved. These results further validate the use of CRPV as an animal model for the study of HPV-mediated disease.
Department of Cancer Research, Merck Research Laboratories, West Point, Pennsylvania 19486.
K M
KM
Haskell
G A
GA
Vuocolo
D
D
Defeo-Jones
R E
RE
Jones
M
M
Ivey-Hoyle
D000595:Amino Acid Sequence; D000818:Animals; D012777:Cottontail rabbit papillomavirus / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D027383:Papillomaviridae / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins; D011485:Protein Binding; D011817:Rabbits; D016160:Retinoblastoma Protein / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
C079183:E7 protein, cottontail rabbit papillomavirus; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D016160:Retinoblastoma Protein; C059731:oncogene protein E7, Human papillomavirus type 16