Nuclear speckle-associated protein Pnn/DRS binds to the transcriptional corepressor CtBP and relieves CtBP-mediated repression of the E-cadherin gene
Nuclear speckle-associated protein Pnn/DRS binds to the transcriptional corepressor CtBP and relieves CtBP-mediated repression of the E-cadherin gene
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DOI：
10.1128/mcb.24.23.10223-10235.2004
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发表时间：
2004-12-01
影响因子：
5.3
通讯作者：
Sugrue, SP
中科院分区：
文献类型：
--
作者：
Alpatov, R;Munguba, GC;Sugrue, SP
以前，我们已经表明，pinin/DRS（Pnn），140 kDa的核和细胞粘附相关的磷蛋白，参与调节细胞粘附和多个肿瘤抑制基因的活性的调制。在细胞核中，Pun集中在“核斑点”中，这是转录和mRNA剪接因子积累的区域，其中Pun参与mRNA加工。另外，Pnn在基因调控中的其他作用尚未确定。通过利用体外下拉试验，在体内相互作用的研究，并结合过表达和RNA干扰实验的免疫荧光，我们提出的证据表明，Pun与已知的转录辅抑制因子CtBP 1相互作用。作为这种相互作用的结果，Pun能够缓解CtBP 1介导的E-钙粘蛋白启动子活性的抑制。我们的研究结果表明，Pun与辅阻遏物CtBP 1的相互作用可能调节CtBP 1对转录的抑制。这种相互作用可能反映了CtBP介导的转录调控和mRNA加工事件中所涉及的偶联因子的存在。
Previously, we have shown that pinin/DRS (Pnn), a 140-kDa nuclear and cell adhesion-related phosphoprotein, is involved in the regulation of cell adhesion and modulation of the activity of multiple tumor suppressor genes. In the nucleus Pun is concentrated in the "nuclear speckles," zones of accumulation of transcriptional and mRNA splicing factors, where Pun is involved in mRNA processing. Alternatively, other roles of Pnn in gene regulation have not yet been established. By utilizing in vitro pull-down assays, in vivo interaction studies, and immunofluorescence in combination with overexpression and RNA interference experiments, we present evidence that Pun interacts with the known transcriptional corepressor CtBP1. As a consequence of this interaction Pun was capable of relieving the CtBP1-mediated repression of E-cadherin promoter activity. Our results suggest that the interaction of Pun with the corepressor CtBP1 may modulate repression of transcription by CtBP1. This interaction may reflect the existence of coupling factors involved in CtBP-mediated transcriptional regulation and mRNA processing events.