The global transcriptional response to transient cell wall damage in Saccharomyces cerevisiae and its regulation by the cell integrity signaling pathway
The global transcriptional response to transient cell wall damage in Saccharomyces cerevisiae and its regulation by the cell integrity signaling pathway
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DOI：
10.1074/jbc.m312954200
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发表时间：
2004-04-09
影响因子：
4.8
通讯作者：
Arroyo, J
中科院分区：
文献类型：
--
作者：
García, R;Bermejo, C;Arroyo, J
在酵母中，破坏细胞壁的环境应激条件导致所谓的“补偿机制”的激活，旨在通过重塑细胞外基质来保持细胞完整性。在这里，我们使用DNA微阵列来研究这种对两种诱导短暂细胞壁损伤的药物反应的分子基础；即刚果红和酶解酶。这两种药物分别上调了132个和101个基因，其中主要的功能群与细胞壁构建和代谢有关。主要反应直到暴露于细胞壁扰动剂数小时后才发生。在某些情况下，这种反应是短暂的，但在其他情况下，特别是在涉及细胞壁重塑的基因的情况下，这种反应更持久。将这些数据与对组成性细胞壁损伤反应的数据聚类，揭示了在所有测试条件下都被强烈诱导的一组共调控基因的存在。细胞壁损伤诱导的基因显示Rlm1p、Crz1p、SBF （Swi4p/ Swi6p）、Msn2p/Msn4p、Ste12p和Tec1p转录因子的DNA结合基元富集，表明该反应具有复杂的调控机制，可能涉及多种信号通路。除PHO89和FKS2外，刚果红诱导的基因在slt2菌株中均未上调。此外，对rlm1突变株对刚果果红的转录反应的表征表明，只有少数基因（PHO89、FKS2、YLR042C和CHA1）至少部分独立于转录因子Rlm1p诱导，其余基因的激活完全依赖于该转录因子。我们的研究结果一致表明，细胞完整性信号通路主要通过Rlm1p介导的转录激活来调节细胞壁损伤补偿反应。
In the yeast Saccharomyces cerevisiae, environmental stress conditions that damage the cell wall lead to activation of the so-called "compensatory mechanism," aimed at preserving cell integrity through a remodeling of this extracellular matrix. Here we used DNA microarrays to investigate the molecular basis of this response to two agents that induce transient cell wall damage; namely Congo Red and Zymolyase. Treatment of the cells with these two agents elicited the up-regulation of 132 and 101 genes respectively, the main functional groups among them being involved in cell wall construction and metabolism. The main response does not occur until hours after exposure to the cell wall-perturbing agent. In some cases, this response was transient, but more sustained in others, especially in the case of the genes involved in cell wall remodeling. Clustering of these data together with those from the response to constitutive cell wall damage, revealed the existence of a cluster of co-regulated genes that was strongly induced under all conditions assayed. Those genes induced by cell wall damage showed an enrichment in DNA binding motifs for Rlm1p, Crz1p, SBF (Swi4p/ Swi6p), Msn2p/Msn4p, Ste12p, and Tec1p transcription factors, suggesting a complex regulation of this response together with the possible involvement of several signaling pathways. With the exception of PHO89 and FKS2, none of the genes induced by Congo Red was up-regulated in a slt2 strain. Moreover, characterization of the transcriptional response to Congo Red in a rlm1 mutant strain revealed that only a few genes (i.e. PHO89, FKS2, YLR042C, and CHA1) were induced at least partially independently of the transcription factor Rlm1p, the rest being totally dependent on this transcription factor for their activation. Our findings consistently demonstrate that the cell integrity signaling pathway regulates the cell wall damage compensatory response, mainly through transcriptional activation mediated by Rlm1p.