Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
Oncogene. 2010 Sep 30;29(39):5427-36. doi: 10.1038/onc.2010.276. Epub 2010 Aug 2.
The nuclear p68 RNA helicase is a prototypical member of the DEAD-box family of RNA helicases. p68 RNA helicase has been implicated in cell proliferation and early organ development and maturation. However, the functional role of p68 RNA helicase in these biological processes at the molecular level is not well understood. We previously reported that tyrosine phosphorylation of p68 RNA helicase mediates the effects of platelet-derived growth factor (PDGF) in induction of epithelial mesenchymal transition by promoting β-catenin nuclear translocation. Here, we report that phosphorylation of p68 RNA helicase at Y593 upregulates transcription of the Snail1 gene. The phosphorylated p68 activates transcription of the Snail1 gene by promoting histone deacetylase (HDAC)1 dissociation from the Snail1 promoter. Our results showed that p68 interacted with the nuclear remodeling and deacetylation complex MBD3:Mi-2/NuRD. Thus, our data suggested that a DEAD-box RNA unwindase could potentially regulate gene expression by functioning as a protein 'displacer' to modulate protein-protein interactions at the chromatin-remodeling complex.
核 p68 RNA 解旋酶是 DEAD 盒家族 RNA 解旋酶的典型成员。p68 RNA 解旋酶已被牵连到细胞增殖和早期器官发育和成熟中。然而,p68 RNA 解旋酶在这些生物学过程中的分子水平上的功能作用还不是很清楚。我们之前报道过,p68 RNA 解旋酶的酪氨酸磷酸化介导血小板衍生生长因子(PDGF)的作用,通过促进β-连环蛋白核转位来诱导上皮间质转化。在这里,我们报告 p68 RNA 解旋酶在 Y593 处的磷酸化上调了 Snail1 基因的转录。磷酸化的 p68 通过促进组蛋白去乙酰化酶(HDAC)1 从 Snail1 启动子上脱离来激活 Snail1 基因的转录。我们的结果表明,p68 与核重塑和去乙酰化复合物 MBD3:Mi-2/NuRD 相互作用。因此,我们的数据表明,一个 DEAD 盒 RNA 解旋酶可以通过作为一种蛋白质“置换物”来调节染色质重塑复合物中的蛋白质-蛋白质相互作用,从而潜在地调节基因表达。