Effect of overexpression of yeast Ppz1 protein phosphatase on gene remodeling in response to changes in carbon source

Our previous results (Calafi et al 2020; PMID: 32339526) demonstrated a defect in cell proliferation when PPZ1 was overexpressed under the control of a tetO-based promoter that was, up to some extent, dependent of the availability of glucose. To further investigate this phenomenon, we have determined the transcriptional response triggered by the shift form high to low glucose, or to galactose, in normal cells and in cells overexpressing PPZ1 from the tetO7–driven multicopy pCM190 plasmid. Our data suggest that, under these circumstances, overexpression of Ppz1 interferes with the proper activation of a set of genes mainly involved in carbon metabolism, thus impairing the normal transcriptional adaptation to conditions in which glucose becomes limiting.我们此前的研究结果（Calafi等人，2020；PMID: 32339526）显示，当PPZ1在基于tetO的启动子调控下过表达时，会引发细胞增殖缺陷，且该缺陷在一定程度上依赖于葡萄糖的可获得性。为进一步探究该现象，我们分别在正常细胞以及由tetO7驱动的多拷贝pCM190质粒介导PPZ1过表达的细胞中，检测了从高葡萄糖环境切换至低葡萄糖环境或半乳糖环境所触发的转录应答。我们的数据表明，在此类条件下，Ppz1的过表达会干扰一组主要参与碳代谢的基因的正常激活，进而损害细胞对葡萄糖受限环境的正常转录适应过程。