E1A proteins are central to the process of transformation by adenovirus. Normally, E1A proteins function during the productive infection of human cells where they greatly stimulate viral gene transcription. In various experimental settings, E1A proteins can also stimulate the transcription of a number of cellular genes. In yet other experimental settings, the expression of E1A proteins has the opposite effect on transcription, inhibiting the activity of transcriptional enhancers. E1A proteins also stimulate DNA synthesis, causing G0-arrested cells to enter the S-phase programme. It is often suggested that transformation may be a consequence of the transcriptional 'transactivating' activity of E1A proteins. That is, E1A proteins might stimulate the expression of cellular genes involved in the transition into S-phase by the same mechanism through which they stimulate early viral transcription. However, recent results on the mechanism of transcriptional transactivation suggest that it may be due to an increase in the activity of general host cell transcription factors. This raises the possibility that transcriptional transactivation is itself a consequence of a larger process which includes the activation of genes encoding transcription factors. Future studies are needed to determine whether E1A proteins activate transcription factors directly, or indirectly through the activation of transcription factor genes. Such studies may indicate whether E1A induced transformation is a consequence of transcriptional transactivation or vice versa.
