The adenoviral E1A oncoprotein activates the Smad7 promoter: Requirement of a functional E-box

摘要

DNA tumorviruses like adenoviruses (AdV) or human papillomaviruses (HPV) have adopted various strategies to interfere with antiproliferative transforming growth factor-β (TGF-β) signalling. Here we report that the AdV E1A oncoprotein is sufficient to induce Smad7 expression, an inhibitor of TGF-β signalling. E1A but not HPV oncoproteins activated the Smad7 promoter. A promoter proximal E-box was crucial for E1A-mediated transcriptional activity. E1A but not HPV oncoproteins induced specific binding activity at this E-box, which was identified as upstream stimulatory factor. In conclusion, these results unravel a novel mechanism of how the AdV E1A oncoprotein induces a cellular inhibitor of TGF-β signalling.