Transcriptional profiling of pH-dependent cell cycle progression. Transcriptional profiling of pH-dependent cell cycle progression

Cells have evolved a complex network of signaling cascades that mediate cellular adaptation to availability of nutrients, growth factors or stress. In these networks, cellular information flow is mostly mediated by posttranslational modifications, most notably phosphorylation, or signaling molecules such as GTPases. However, genetic analysis has also implicated a number of proton transporters in regulating cellular signaling processes. Here, we report the transcriptional response of starved cells upon stimulation with serum and glucose upon inhibition of Sodium Hydrogen Exchangers and compare these responses to inhibition of cycle progression with the p300/CBP inhibitor C646. Overall design: The gene expression profile of starved cells and starved cells stimulated with FCS and glucose for 4 hours in the presence of Dimethyl Amiliride (DMA, 100µM), C646 (10µM) or DMSO only, was compared by Illumina sequencing.

细胞已演化出一套复杂的信号级联反应网络，可介导细胞对营养物质、生长因子的可获得性或应激状态产生适应性应答。在这类网络中，细胞内的信息传递主要通过翻译后修饰（posttranslational modifications）——尤以磷酸化最为典型——或GTP酶等信号分子介导。然而，遗传学研究亦证实多种质子转运蛋白参与调控细胞信号转导过程。
本研究报道了钠氢交换体（Sodium Hydrogen Exchangers）抑制条件下，饥饿细胞经血清与葡萄糖刺激后的转录应答情况，并将该应答与采用p300/CBP抑制剂C646抑制细胞周期进程所产生的应答进行了对比。
实验设计：本研究采用Illumina测序技术，对比分析了饥饿细胞，以及在100μM二甲基阿米洛利（Dimethyl Amiliride, DMA）、10μM C646或仅二甲基亚砜（DMSO）存在时，经胎牛血清（FCS）与葡萄糖刺激4小时的饥饿细胞的基因表达谱。