Homologous sequences in adenovirus Ela and human papillomavirus E7 proteins mediate interaction with the same set of cellular proteins

Studies of adenovirus EIA oncoprotein mutants suggest that the association of ElA with the retinoblastoma protein (pRB) is necessary for ElA-mediated transformation. Mutational analysis of ELA indicates that two regions of pRB are required for ELA to form stable complexes with the retinoblastoma protein. In addition to pRB binding, these regions are necessary for ElA association with several other cellular proteins, including p130, p107, cycin A, and p33cdk2. Here we show that short synthetic peptides containing the pRB-binding sequences of E1A are sufficient for interaction with p107, cyclin A, and p130. The E7 protein of human papillomavirus type 16 contains an element that binds to pRB and appears to be functionally homologous to the ElA sequences. Peptides containing this region of the E7 protein were able to interact with p107, cyclin A, and p130 in addition to pRB. These findings suggest that the common mechanism of transformation used by these viral oncogenes involves their association with a set of polypeptides. The adenovirus ElA oncoprotein has pleiotropic effects on cell proliferation. These changes appear to be mediated, at least in part, by the association of ElA with several cellular proteins. Stable protein complexes are readily de-tected in adenovirus-infected or-transformed cells (29, 58)