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.
Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institutet, Stockholm, Sweden.
G M
GM
Wahlström
B
B
Vennström
M B
MB
Bolin
D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D006801:Humans; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms; D011988:Receptors, Thyroid Hormone / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D017500:Adenovirus E1A Proteins; D020033:Protein Isoforms; D011988:Receptors, Thyroid Hormone; D011994:Recombinant Proteins; D018995:Myosin Heavy Chains