Programa de Recerca en Càncer, IMIM-Hospital del Mar, E-08003, Barcelona, Spain.
J Cell Sci. 2011 Dec 15;124(Pt 24):4161-71. doi: 10.1242/jcs.078824. Epub 2012 Jan 5.
Snail1 is a transcriptional repressor of E-cadherin that triggers epithelial-mesenchymal transition (EMT). Here, we report assisted Snail1 interaction with the promoter of a typical mesenchymal gene, fibronectin (FN1), both in epithelial cells undergoing EMT and in fibroblasts. Together with Snail1, the p65 subunit of NF-κB and PARP1 bound to the FN1 promoter. We detected nuclear interaction of these proteins and demonstrated the requirement of all three for FN1 transcription. Moreover, other genes involved in cell movement mimic FN1 expression induced by Snail1 or TGF-β1 treatment and recruit p65NF-κB and Snail1 to their promoters. The molecular cooperation between Snail1 and NF-κB in transcription activation provides a new insight into how Snail1 can modulate a variety of cell programs.
蜗牛 1 是 E-钙粘蛋白的转录抑制剂，能引发上皮间质转化（EMT）。在这里，我们报告蜗牛 1 协助与典型间充质基因纤维连接蛋白（FN1）的启动子相互作用，这一过程发生在 EMT 中的上皮细胞和成纤维细胞中。与蜗牛 1 一起，NF-κB 的 p65 亚基和 PARP1 结合到 FN1 启动子上。我们检测到这些蛋白质的核相互作用，并证明了这三种蛋白质对于 FN1 转录的必要性。此外，其他参与细胞运动的基因模仿由蜗牛 1 或 TGF-β1 处理诱导的 FN1 表达，并招募 p65NF-κB 和蜗牛 1 到它们的启动子上。蜗牛 1 和 NF-κB 在转录激活中的分子合作提供了一个新的视角，了解蜗牛 1 如何能够调节多种细胞程序。
