Saccharomyces cerevisiae phospholipase C regulates transcription of Msn2p-dependent stress-responsive genes
Saccharomyces cerevisiae phospholipase C regulates transcription of Msn2p-dependent stress-responsive genes
复制标题
DOI：
10.1128/ec.00438-07
复制
发表时间：
2008-06-01
期刊：
影响因子：
--
通讯作者：
Vancura, Ales
中科院分区：
文献类型：
--
作者：
Demczuk, Agnieszka;Guha, Nilanjan;Vancura, Ales
磷酸磷脂酰肌醇参与信号转导、细胞骨架组织和膜运输。肌醇多磷酸盐由磷脂酰肌醇磷酸盐通过磷脂酶 C 依赖性途径产生，可调节染色质重塑。我们使用全基因组表达分析来进一步研究 Plc1p（酿酒酵母中磷酸肌醇特异性磷脂酶 C）和肌醇多磷酸在转录调控中的作用。 Plc1p 有助于调节在丰富培养基中生长的细胞中大约 2% 的酵母基因。大多数这些基因是由营养限制和其他环境压力诱导的，并且在 plc1 Delta 细胞中被去抑制。令人惊讶的是，Plc1p 调控的基因与 Swi/Snf 或 RSC 染色质重塑复合物调控的基因集不相关，但与 Msn2p 控制的基因相关。我们的结果表明，plc1 Delta 细胞中应激反应基因表达的增加是由环 AMP 合成减少和蛋白激酶 A (PKA) 介导的 Msn2p 磷酸化以及 Msn2p 与应激反应启动子的结合增加介导的。因此，plc1 Delta 细胞显示出 PKA 活性降低的细胞的其他表型特征。我们的结果与模型一致，其中 Plc1p 与膜受体 Gpr1p 和相关的 G(α) 蛋白 Gpa2p 在与 Ras1p/Ras2p 分开并汇聚于 PKA 的途径中共同作用。
Phosphatidylinositol phosphates are involved in signal transduction, cytoskeletal organization, and membrane trafficking. Inositol polyphosphates, produced from phosphatidylinositol phosphates by the phospholipase C-dependent pathway, regulate chromatin remodeling. We used genome-wide expression analysis to further investigate the roles of Plc1p (phosphoinositide-specific phospholipase C in Saccharomyces cerevisiae) and inositol polyphosphates in transcriptional regulation. Plc1p contributes to the regulation of approximately 2% of yeast genes in cells grown in rich medium. Most of these genes are induced by nutrient limitation and other environmental stresses and are derepressed in plc1 Delta cells. Surprisingly, genes regulated by Plc1p do not correlate with gene sets regulated by Swi/Snf or RSC chromatin remodeling complexes but show correlation with genes controlled by Msn2p. Our results suggest that the increased expression of stress-responsive genes in plc1 Delta cells is mediated by decreased cyclic AMP synthesis and protein kinase A (PKA)-mediated phosphorylation of Msn2p and increased binding of Msn2p to stress-responsive promoters. Accordingly, plc1 Delta cells display other phenotypes characteristic of cells with decreased PKA activity. Our results are consistent with a model in which Plc1p acts together with the membrane receptor Gpr1p and associated G(alpha) protein Gpa2p in a pathway separate from Ras1p/Ras2p and converging on PKA.