Kannan P, Yu Y, Wankhade S, Tainsky M A
Rammelkamp Center for Education and Research, MetroHealth Campus, Case Western Reserve University,2500 MetroHealth Drive, Cleveland, OH 44109, USA.
Nucleic Acids Res. 1999 Feb 1;27(3):866-74. doi: 10.1093/nar/27.3.866.
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.
转录因子AP - 2的过表达与含有激活型ras癌基因的人畸胎瘤细胞系PA - 1的致瘤性有关。在此我们提供证据表明，AP - 2的过表达会隔离转录共激活因子，从而导致自我抑制。我们鉴定了与AP - 2相互作用的蛋白，并确定这些蛋白是否为AP - 2介导转录的共激活因子。其中一种相互作用蛋白是聚ADP - 核糖聚合酶（PARP）。PARP抑制PA - 1细胞中AP - 2的自我抑制并增强其活性，表明它是AP - 2转录的共激活因子。PARP能显著恢复ras癌基因转化细胞中AP - 2的转录活性，提示它可能抑制这些细胞的转化。另一种与AP - 2相互作用的蛋白RAP74，是转录因子TFIIF的一个亚基，它单独或与TFIIF的另一个亚基RAP30共同存在时，均不影响AP - 2介导的转录激活。RAP74也不能缓解AP - 2介导的转录自我干扰和交叉干扰。这些研究表明，AP - 2与RAP74之间的相互作用可能具有除激活AP - 2介导的转录之外的其他功能。
