MNL1 regulates weak acid-induced stress responses of the fungal pathogen Candida albicans.
MNL1 regulates weak acid-induced stress responses of the fungal pathogen Candida albicans.
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DOI：
10.1091/mbc.e07-09-0946
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发表时间：
2008-10
影响因子：
3.3
通讯作者：
M. Ramsdale;L. Selway;D. Stead;Janet Walker;Zhikang Yin;S. Nicholls;J. Crowe;E. Sheils;A. J. Brown
中科院分区：
文献类型：
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作者：
M. Ramsdale;L. Selway;D. Stead;Janet Walker;Zhikang Yin;S. Nicholls;J. Crowe;E. Sheils;A. J. Brown
MNL 1是一种孤儿Msn 2样基因（酿酒酵母中的YER 130 c）的白色念珠菌同源物，没有已知的功能。在这里，我们报告MNL 1调节弱酸胁迫反应。MNL 1的缺失阻止了C.白色念珠菌细胞的弱酸应力和妥协，他们的整体转录反应在这些条件下。Mnl 1依赖基因的启动子包含一个新的STRE-like元件（SLE），该元件将Mnl 1依赖的弱酸胁迫诱导的转录强加给C.白色念珠菌。SLE（HHYYCCCCTTYTY）与转录抑制因子Nrg 1识别的Nrg 1反应元件（NRE）元件相关。NRG 1的缺失部分恢复了C.白色念珠菌mnl 1细胞适应弱酸应激，表明Mnl 1和Nrg 1具有拮抗作用来调节这种反应。分子，微阵列和蛋白质组学分析表明，MnL 1依赖的适应不会发生在细胞暴露于促凋亡或pronecrotic剂量的弱酸，这表明Ras-通路激活可能会抑制MnL 1依赖的弱酸反应在垂死的细胞。我们的工作定义了这个YER 130 c同源基因在应激适应和细胞死亡中的作用。
MNL1, the Candida albicans homologue of an orphan Msn2-like gene (YER130c in Saccharomyces cerevisiae) has no known function. Here we report that MNL1 regulates weak acid stress responses. Deletion of MNL1 prevents the long-term adaptation of C. albicans cells to weak acid stresses and compromises their global transcriptional response under these conditions. The promoters of Mnl1-dependent genes contain a novel STRE-like element (SLE) that imposes Mnl1-dependent, weak acid stress-induced transcription upon a lacZ reporter in C. albicans. The SLE (HHYYCCCCTTYTY) is related to the Nrg1 response element (NRE) element recognized by the transcriptional repressor Nrg1. Deletion of NRG1 partially restores the ability of C. albicans mnl1 cells to adapt to weak acid stress, indicating that Mnl1 and Nrg1 act antagonistically to regulate this response. Molecular, microarray, and proteomic analyses revealed that Mnl1-dependent adaptation does not occur in cells exposed to proapoptotic or pronecrotic doses of weak acid, suggesting that Ras-pathway activation might suppress the Mnl1-dependent weak acid response in dying cells. Our work defines a role for this YER130c orthologue in stress adaptation and cell death.