Transcriptional and Transforming Activities of the Adenovirus E1A Proteins

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The products of the adenovirus E1A gene play key roles in both the productive and transforming cycles of infection. During productive growth in human cells, the E1A proteins activate expression of adenovirus genes at the level of transcription. The E1A proteins are also oncoproteins that cooperate with the adenovirus E1B gene products to oncogenically transform rodent cells. The 289R E1A protein is primarily responsible for the transactivation of viral gene expression. This protein and CR3 peptide stimulate transcription when added to uninfected cell-nuclear extracts in vitro. It is, therefore, unlikely that transactivation is generally a result of E1A protein-induced increases in the absolute concentration of cellular transcriptional components. A mechanism invoking E1A protein-dependent modification of cellular transcriptional components to increase one or more of their activities has a number of virtues. The E1A gene has been reported to transform established NIH 3T3 cells in the absence of a cooperating oncogene when it is expressed at high levels under the control of a heterologous promoter. However, the results obtained with established cell lines are difficult to interpret because such lines may harbor mutant recessive oncogenes, such as p53, that could influence the transforming activity of E1A proteins.

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