PolyADP-ribose polymerase is a coactivator for AP-2-mediated transcriptional activation

Overexpression of transcription factor AP-2 has been implicated in the tumo rigenicity of the human teratocarcinoma cell lines PA-1 that contain an act ivated ras oncogene. Here we show evidence that overexpression of AP-2 sequ esters transcriptional coactivators which results in self-inhibition. We id entified AP-2-interacting proteins and determined whether these proteins we re coactivators for AP-2-mediated transcription. One such interacting prote in is polyADP-ribose polymerase (PARP). PARP suppresses AP-2 self-inhibitio n and enhances AP-2 activity in PA-1 cells indicating that it is a coactiva tor for AP-2-transcription. PARP significantly restores AP-2 transcriptiona l activity in ras oncogene-transformed cells suggesting that it might suppr ess transformation in these cells. Another AP-2-interacting protein, RAP74, a subunit of transcription factor TFIIF, does not affect AP-2-mediated tra nscriptional activation alone or in the presence of RAP30, the other subuni t of TFIIF. RAP74 also fails to relieve AP-2-mediated transcriptional self- interference and cross-interference. These studies suggest that the interac tion between AP-2 and RAP74 may have functions other than activation of AP- 2-mediated transcription.