title: PolyADP-ribose polymerase is a coactivator for AP-2-mediated transcriptional activation.
abstract: Overexpression of transcription factor AP-2 has been implicated in the tumorigenicity of the human teratocarcinoma cell lines PA-1 that contain an activated ras oncogene. Here we show evidence that overexpression of AP-2 sequesters transcriptional coactivators which results in self-inhibition. We identified AP-2-interacting proteins and determined whether these proteins were coactivators for AP-2-mediated transcription. One such interacting protein is polyADP-ribose polymerase (PARP). PARP suppresses AP-2 self-inhibition and enhances AP-2 activity in PA-1 cells indicating that it is a coactivator for AP-2-transcription. PARP significantly restores AP-2 transcriptional activity in ras oncogene-transformed cells suggesting that it might suppress transformation in these cells. Another AP-2-interacting protein, RAP74, a subunit of transcription factor TFIIF, does not affect AP-2-mediated transcriptional activation alone or in the presence of RAP30, the other subunit of TFIIF. RAP74 also fails to relieve AP-2-mediated transcriptional self-interference and cross-interference. These studies suggest that the interaction between AP-2 and RAP74 may have functions other than activation of AP-2-mediated transcription.
authors.affiliation: Rammelkamp Center for Education and Research, MetroHealth Campus, Case Western Reserve University,2500 MetroHealth Drive, Cleveland, OH 44109, USA. pkannan@research.mhmc.org
authors.forename: P
authors.initials: P
authors.lastname: Kannan
authors.forename: Y
authors.initials: Y
authors.lastname: Yu
authors.forename: S
authors.initials: S
authors.lastname: Wankhade
authors.forename: M A
authors.initials: MA
authors.lastname: Tainsky
mesh_terms: D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism; D006801:Humans; D010449:Peptide Mapping; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators / Q000378:metabolism; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism*; D019473:Transcription Factors, TFII; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; C070633:Gal-VP16; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D019473:Transcription Factors, TFII; D011065:Poly(ADP-ribose) Polymerases; C056604:transcription factor TFIIF