The adenoviral E1A oncoprotein activates the Smad7 promoter: requirement of a functional E-box.
DNA tumorviruses like adenoviruses (AdV) or human papillomaviruses (HPV) have adopted various strategies to interfere with antiproliferative transforming growth factor-beta (TGF-beta) signalling. Here we report that the AdV E1A oncoprotein is sufficient to induce Smad7 expression, an inhibitor of TGF-beta 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-beta signalling.
Dole
Vandana S
VS
Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
Smola
Hans
H
Dooley
Steven
S
Said
Harun M
HM
Oldak
Monika
M
Pfister
Herbert J
HJ
Smola
Sigrun
S
D017500:Adenovirus E1A Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral / Q000502:physiology*; D024721:E-Box Elements / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D027383:Papillomaviridae; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D051906:Smad7 Protein / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism
D017500:Adenovirus E1A Proteins; C497806:SMAD7 protein, human; D051906:Smad7 Protein; D016212:Transforming Growth Factor beta