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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A coactivator trap identifies NONO (p54~(nrb)) as a component of the cAMP-signaling pathway
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A coactivator trap identifies NONO (p54~(nrb)) as a component of the cAMP-signaling pathway

机译：辅助激活器陷阱将NONO（p54〜（nrb））识别为cAMP信号通路的组成部分

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摘要

Signal transduction pathways often use a transcriptional component to mediate adaptive cellular responses. Coactivator proteins function prominently in these pathways as the conduit to the basic transcriptional machinery. Here we present a high-throughput cell-based screening strategy, termed the "coactivator trap," to study the functional interactions of coactivators with transcription factors. We applied this strategy to the cAMP signaling pathway, which utilizes two families of coactivators, the cAMP response element binding protein (CREB) binding protein (CBP)/p300 family and the recently identified transducers of regulated CREB activity family (TORCs1-3). In addition to identifying numerous known interactions of these coactivators, this analysis identified NONO (p54~(nrb)) as a TORC-interacting protein. RNA interference experiments demonstrate that NONO is necessary for cAMP-dependent activation of CREB target genes in vivo. Furthermore, TORC2 and NONO complex on cAMP-responsive promoters, and NONO acts as a bridge between the CREB/TORC complex and RNA polymerase II. These data demonstrate the utility of the coactivator trap by identification of a component of cAMP-mediated transcription.
机译：信号转导途径通常使用转录成分来介导适应性细胞反应。辅激活蛋白在这些途径中起着重要的作用，成为通往基本转录机制的通道。在这里，我们提出了一种基于细胞的高通量筛选策略，称为“共激活因子陷阱”，以研究共激活因子与转录因子的功能相互作用。我们将此策略应用于cAMP信号传导途径，该途径利用了两个共激活因子家族，即cAMP反应元件结合蛋白（CREB）结合蛋白（CBP）/ p300家族和最近鉴定的CREB活性家族（TORCs1-3）的传感器。除了确定这些共激活剂的众多已知相互作用外，该分析还确定了NONO（p54〜（nrb））为TORC相互作用蛋白。 RNA干扰实验表明NONO对于体内cAMP依赖性CREB靶基因的激活是必需的。此外，TORC2和NONO复合物位于cAMP响应启动子上，而NONO充当CREB ​​/ TORC复合物与RNA聚合酶II之间的桥梁。这些数据通过鉴定cAMP介导的转录成分证明了共激活因子陷阱的实用性。

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