Homologous sequences in adenovirus E1A and human papillomavirus E7 proteins mediate interaction with the same set of cellular proteins.
Studies of adenovirus E1A oncoprotein mutants suggest that the association of E1A with the retinoblastoma protein (pRB) is necessary for E1A-mediated transformation. Mutational analysis of E1A indicates that two regions of pRB are required for E1A to form stable complexes with the retinoblastoma protein. In addition to pRB binding, these regions are necessary for E1A association with several other cellular proteins, including p130, p107, cyclin 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 E1A 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.
Dyson
N
N
Massachusetts General Hospital Cancer Center, Charlestown 02129.
Guida
P
P
Münger
K
K
Harlow
E
E
D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D000260:Adenoviruses, Human / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001667:Binding, Competitive; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000302:isolation & purification / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D027383:Papillomaviridae / Q000235:genetics / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins; D010449:Peptide Mapping; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D017500:Adenovirus E1A Proteins; D009363:Neoplasm Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D010455:Peptides; C059731:oncogene protein E7, Human papillomavirus type 16