Corepressor CtBP and nuclear speckle protein Pnn/DRS differentially modulate transcription and splicing of the E-cadherin gene
Corepressor CtBP and nuclear speckle protein Pnn/DRS differentially modulate transcription and splicing of the E-cadherin gene
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DOI：
10.1128/mcb.00421-07
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发表时间：
2008-03-01
影响因子：
5.3
通讯作者：
Sugrue, Stephen P.
中科院分区：
文献类型：
--
作者：
Alpatov, Roman;Shi, Yujiang;Sugrue, Stephen P.
CtBP是一种具有致瘤潜力的转录辅抑制因子，靶向肿瘤抑制基因E-cadherin的启动子。Pnn/DRS（Pnn）是一种“核斑点”相关蛋白，参与mRNA加工以及通过与CtBP结合来调节E-钙粘蛋白的转录。在这里，我们表明，CtBP可以招募Pun CtBP相关的复合物，导致Pnn依赖的染色质重塑在E-钙粘蛋白启动子。此外，CtBP和潘可以差异调节E-钙粘蛋白mRNA剪接，聚合酶II在此事件中作为一个接口。因此，Pnn/CtBP功能相互作用代表了一种新的机制，将辅阻遏物CtBP和Pnn与主要肿瘤抑制基因的转录偶联mRNA剪接联系起来。我们的研究结果暗示存在参与肿瘤发生的分子开关，其协调启动子特异性事件和mRNA加工，通过在基因启动子和mRNA剪接机器内的调节复合物之间充当桥接元件。
CtBP is a transcriptional corepressor with tumorigenic potential that targets the promoter of the tumor suppressor gene E-cadherin. Pnn/DRS (Pnn) is a "nuclear speckle"-associated protein involved in mRNA processing as well as transcriptional regulation of E-cadherin via its binding to CtBP. Here, we show that CtBP can recruit Pun to CtBP-associated complexes, resulting in Pnn-dependent chromatin remodeling at the E-cadherin promoter. In addition, CtBP and Pan can differentially modulate E-cadherin mRNA splicing, with polymerase II serving as an interface in this event. Therefore, the Pnn/CtBP functional interplay represents a novel mechanism linking the corepressor CtBP and Pnn to the transcription-coupled mRNA splicing of a major tumor suppressor gene. Our findings implicate the existence of the molecular switches involved in tumorigenesis, which coordinate promoter-specific events and mRNA processing, by serving as bridging elements between the regulatory complexes both at gene promoters and within the mRNA splicing machineries.