The E7 oncoprotein associates with Mi2 and histone deacetylase activity topromote cell growth

E7 is the main transforming protein of human papilloma virus type 16 (HPV16 ) which is implicated in the formation of cervical cancer. The transforming activity of E7 has been attributed to its interaction with the retinoblast oma (Rb) tumour suppressor. However, Rb binding is not sufficient for trans formation by E7, Mutations within a zinc finger domain, which is dispensabl e for Rb binding, also abolish E7 transformation functions. Here we show th at HPV16 E7 associates with histone deacetylase in vitro and in vivo, via i ts zinc finger domain. Using a genetic screen, we identify Mi2 beta, a comp onent of the recently identified NURD histone deacetylase complex, as a pro tein that binds directly to the E7 zinc finger. A zinc finger point mutant which is unable to bind Mi2 beta and histone deacetylase but is still able to bind Rb fails to overcome cell cycle arrest in osteosarcoma cells. Our r esults suggest that the binding to a histone deacetylase complex is an impo rtant parameter for the growth-promoting activity of the human papilloma vi rus E7 protein. This provides the first indication that viral oncoproteins control cell proliferation by targeting deacetylation pathways.