GC-binding factor 2 interacts with Dishevelled and regulates Wnt signaling pathways in human carcinoma cell lines
GC-binding factor 2 interacts with Dishevelled and regulates Wnt signaling pathways in human carcinoma cell lines
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DOI：
10.1002/ijc.25837
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发表时间：
2011-10-01
影响因子：
6.4
通讯作者：
Johnson, Alfred C.
中科院分区：
文献类型：
--
作者：
Ohtsuka, Hideo;Oikawa, Masaya;Johnson, Alfred C.
gc结合因子2 （GCF2）是一种降低几种基因活性的转录抑制因子，能够直接结合EGFR启动子中富含gc的序列并抑制EGFR的转录活性。除了作为转录抑制因子的功能外，GCF2还可以直接与其他蛋白如flightless-1 （Fli-1）相互作用。先前关于Fli-1功能的许多发现表明，Fli-1在参与信号转导途径的分子和肌动蛋白细胞骨架之间提供直接联系。我们假设GCF2和Fli-1一起在调节细胞骨架功能、细胞迁移和/或形态中发挥作用。在我们的研究中，我们观察到GCF2对于RhoA的激活至关重要，RhoA是一种小的GTPase，在肌动蛋白细胞骨架的调节中起关键作用。由于GCF2表达降低，RhoA明显失活。随后进行共免疫沉淀以进一步研究抑制功能的机制。我们发现disheveled （Dvl）是Wnt通路的关键介质，是GCF2的结合伙伴。这些结果强烈提示GCF2在wnt -非规范平面细胞极性（PCP）信号通路中发挥作用。因此，GCF2可能通过dvl和RhoA调控细胞骨架或迁移。
GC-binding factor 2 (GCF2), a transcriptional repressor that decreases the activity of several genes is capable of binding directly to the GC-rich sequence of the EGFR promoter and repressing the transcriptional activity of EGFR. In addition to its function as a transcriptional repressor, GCF2 can directly interact with other proteins such as flightless-1 (Fli-1). Many previous findings pertaining to the function of Fli-1 have suggested a role for fli-1 in providing a direct link between molecules involved in signal transduction pathways and the actin cytoskeleton. We hypothesized that GCF2, together with Fli-1, plays a role in regulating cytoskeleton function, cell migration, and/or morphology. In our study, we observed that GCF2 is crucial for the activation of RhoA, a small GTPase that plays a key role in the regulation of the actin cytoskeleton. RhoA was markedly inactivated as a result of the decreased expression of GCF2. Co-immunoprecipitations were subsequently performed to further investigate the mechanism for the repressive function. We identified dishevelled (Dvl), which is the key mediator for the Wnt pathway, as a binding partner with GCF2. These results strongly suggest that GCF2 plays a role in the Wnt-noncanonical planar cell polarity (PCP) signaling pathway. Consequently, GCF2 may regulate the cytoskeleton or migration via Dvls and RhoA.