Targeting the MEF2-like transcription factor Smp1 by the stress-activated Hog1 mitogen-activated protein kinase
Targeting the MEF2-like transcription factor Smp1 by the stress-activated Hog1 mitogen-activated protein kinase
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DOI：
10.1128/mcb.23.1.229-237.2003
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发表时间：
2003-01-01
影响因子：
5.3
通讯作者：
Posas, F
中科院分区：
文献类型：
--
作者：
de Nadal, E;Casadomé, L;Posas, F
暴露的酿酒酵母细胞外渗透压的增加激活应激激活的Hog 1丝裂原活化蛋白激酶（MAPK），这是必不可少的细胞存活后渗透压。酵母细胞通过诱导大量基因的表达来响应渗透胁迫，并且Hog 1 MAPK在胁迫后的基因转录中起关键作用。为了了解Hog 1如何控制基因表达，我们设计了一个遗传筛选来分离MAPK控制下的新转录因子，并确定了MEF 2样转录因子Smp 1作为Hog 1的靶点。SMP 1的过表达诱导Hog 1依赖性的表达，如STL 1，而smp 1Delta细胞在其表达中有缺陷。一致地，smp 1Delta细胞在渗透压休克后显示出活力降低。在体内共沉淀和磷酸化的研究表明，Smp 1和Hog 1相互作用，Smp 1是磷酸化后，渗透压胁迫在Hog 1依赖的方式。Hog 1在体外磷酸化Smp 1的C-末端区域。Smp 1被MAPK磷酸化对其功能至关重要，因为不能被MAPK磷酸化的突变等位基因显示受损的应激反应。因此，我们的数据表明，Smp 1的行为下游的Hog 1，控制一个子集的MAPK诱导的反应。此外，SMP 1在稳定期集中在细胞核中，缺乏SMPI导致细胞在稳定期失去活力。Smp 1的定位依赖于HOG 1，并且一贯地，hog 1 Delta细胞在此生长阶段也失去活力。这些数据表明，Smp 1可能是介导的作用，为Hog 1 MAPK在稳定期。
Exposure of Saccharomyces cerevisiae to increases in extracellular osmolarity activates the stress-activated Hog1 mitogen-activated protein kinase (MAPK), which is essential for cell survival upon osmotic stress. Yeast cells respond to osmotic stress by inducing the expression of a very large number of genes, and the Hog1 MAPK plays a critical role in gene transcription upon stress. To understand how Hog1 controls gene expression, we designed a genetic screen to isolate new transcription factors under the control of the MAPK and identified the MEF2-like transcription factor, Smp1, as a target for Hog1. Overexpression of SMP1 induced Hog1-dependent expression of osmoresponsive genes such as STL1, whereas smp1Delta cells were defective in their expression. Consistently, smp1Delta cells displayed reduced viability upon osmotic shock. In vivo coprecipitation and phosphorylation studies showed that Smp1 and Hog1 interact and that Smp1 is phosphorylated upon osmotic stress in a Hog1-dependent manner. Hog1 phosphorylated Smp1 in vitro at the C-terminal region. Phosphorylation of Smp1 by the MAPK is essential for its function, since a mutant allele unable to be phosphorylated by the MAPK displays impaired stress responses. Thus, our data indicate that Smp1 acts downstream of Hog1, controlling a subset of the responses induced by the MAPK. Moreover, Smp1 concentrates in the nucleus during the stationary phase, and the lack of SMPI results in cells that lose viability in the stationary phase. Localization of Smp1 depends on HOG1, and consistently, hog1Delta cells also lose viability during this growth phase. These data suggest that Smp1 could be mediating a role for the Hog1 MAPK during the stationary phase.