Comparison of the binding of the human papillomavirus type 16 and cottontail rabbit papillomavirus E7 proteins to the retinoblastoma gene product

Abstract

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.