PolyADP-ribose polymerase is a coactivator for AP-2-mediated transcriptional activation
PolyADP-ribose polymerase is a coactivator for AP-2-mediated transcriptional activation
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DOI：
10.1093/nar/27.3.866
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发表时间：
1999-02-01
影响因子：
14.9
通讯作者：
Tainsky, MA
中科院分区：
文献类型：
--
作者：
Kannan, P;Yu, YH;Tainsky, MA
转录因子AP-2的过表达与含有激活的ras癌基因的人畸胎癌细胞系PA-1的致瘤性有关。在这里，我们证明AP-2的过度表达隔离了转录共激活因子，从而导致了自我抑制。我们鉴定了AP-2相互作用的蛋白，并确定这些蛋白是否是AP-2介导的转录的共激活因子。其中一种相互作用的蛋白质是聚腺苷二磷酸核糖聚合酶(PARP)。PARP抑制PA-1细胞中AP-2的自我抑制并增强AP-2的活性，表明其是AP-2转录的共激活因子。PARP显着恢复ras癌基因转化细胞的AP-2转录活性，提示其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，它不影响AP-2介导的转录激活，也不影响TFIIF的另一个亚基RAP30的存在。RAP74也不能解除AP-2介导的转录自我干扰和交叉干扰。这些研究表明，AP-2和RAP74之间的相互作用可能具有激活AP-2介导的转录以外的其他功能。
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.