E1a revisited: The case for multiple cooperative trans-activation domains

Products encoded in the E1a oncogene of adenoviruses are required to activate transcription of all viral early genes and some cellular genes. A current interpretation of experimental data supports the hypothesis that this ''trans-activation'' is mediated solely by a block of amino acids known as conserved domain 3, which is unique to the largest E1a protein, while the remaining E1a protein sequences contain discrete domains required for functions other than trans-activation. However, there is also considerable evidence inconsistent with this simple model of E1a structure and function. Both of the major E1a proteins appear to participate in trans-activation by three different types of interaction with cellular transcription factors and other regulatory proteins. In this review we attempt to rationalize the experimental data and provide a more integrated view of E1a structure and function.