The Adenovirus E1A Protein Is a Potent Coactivator for Thyroid Hormone Receptors

The thyroid hormone receptors interact with several different cofactors when activating transciption. In this study, we show that the adenovirus E1A oncoprotein functions as a strong coactivator for the thyroid hormone receptor (TR), and that TR and E1A synergistically activate transcription via direct (DR4) or palindromic (IRO) hormone-responsive sites. Cotransfection experiments using different isoforms of the chicken TR and E1A show synergistic, ligand-enhanced transactivation. This transactivation is accomplished through a direct, ligand-independent interaction between TR and E1A. The interaction domains in TR are localized to the DNA-binding domain and to the carboxy-terminal part of the ligand-binding domain. In E1A, the regions of interactions are localized to the conserved regions 1 and 3. Both of these domains in E1A are required for a 40-fold enhancement of TR-mediated activation in transfection experiments. Taken together, we show that E1A strongly enhances transcriptional activation, which suggests that it serves as a bridging factor between the receptor and other components of the transcription machinery.