Cell transformation by the E7 oncoprotein of human papillomavirus type 16: interactions with nuclear and cytoplasmic target proteins.

The E7 oncoprotein of human papillomavirus type 16 (HPV-16) has long been known as a potent immortalizing and transforming agent. However, the molecular mechanisms underlying cell transformation and immortalization by E7 remain largely unknown. It is believed that E7 exerts its oncogenic function at least in part by modulating cellular growth regulatory pathways. Increasing experimental evidence suggests that cell transformation by E7 is mediated by the physical association of E7 with cellular regulatory proteins, whose functions are specifically altered by E7, as exemplified by the well-known interaction of E7 with the retinoblastoma protein. In this review, we summarize the available data on the interaction of E7 with cellular regulatory factors and functional consequences of these interactions. We will focus the review on a set of recently identified new target proteins for the E7 oncoprotein, which sheds new light on E7 functions required for cell transformation and immortalization. Similar to the case of the E6 protein of HPV-16, whose interaction with p53 was long considered its major activity, it now appears that the interaction of E7 with the retinoblastoma protein represents just one of many distinct interactions that are relevant for cell transformation.