ADENOVIRUS-E1A PROTEINS TRANSFORM CELLS BY SEQUESTERING REGULATORY PROTEINS

Cell transformation by adenovirus-E1A proteins is mediated by binding to cellular proteins whose functions are thereby inactivated or altered. The various properties of the E1A proteins are reviewed in relation to their binding to cellular proteins. A number of the cellular proteins which associate to E1A have been identified: the retinoblastoma-susceptibility protein (Rb), the p107 protein, cyclin A and the p33cdk2 kinase. Recent data have shown that those proteins are also able to bind to transcription factor E2F. Binding of Rb to E2F represses the transcription-activating potential of E2F. E1A can sequester the regulatory proteins, like Rb, and thereby release free, active E2F. The domains in E1A that are essential for this transcriptional regulation are also required for the transforming properties of E1A.