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葡萄糖饥饿和 Ca 对酿酒酵母 GPX1 表达的调控机制:Snf1 和 Ras/cAMP 途径在 Ca 信号转导中的作用。

Regulatory mechanism for expression of GPX1 in response to glucose starvation and Ca in Saccharomyces cerevisiae: involvement of Snf1 and Ras/cAMP pathway in Ca signaling.

机构信息

Laboratory of Molecular Microbiology, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan.

出版信息

Genes Cells. 2010 Jan;15(1):59-75. doi: 10.1111/j.1365-2443.2009.01365.x. Epub 2009 Dec 9.

Abstract

Saccharomyces cerevisiae has three homologues of the glutathione peroxidase gene, GPX1, GPX2, and GPX3. We have previously reported that the expression of GPX3 was constitutive, but that of GPX2 was induced by oxidative stress and CaCl(2), and uncovered the regulatory mechanisms involved. Here, we show that the expression of GPX1 is induced by glucose starvation and treatment with CaCl(2). The induction of GPX1 expression in response to glucose starvation and Ca(2+) was dependent on the transcription factors Msn2 and Msn4 and cis-acting elements [stress response element (STRE)] in the GPX1 promoter. The Ras/cAMP pathway is also involved in the expression of GPX1. We found that Snf1, a Ser/Thr protein kinase, is involved in the glucose starvation- and Ca(2+)-induced expression of GPX1. The activation of Snf1 is accompanied by phosphorylation of Thr(210). We found that the Ca(2+)-treatment as well as glucose starvation causes the phosphorylation of Thr(210) of Snf1 in a Tos3, Sak1, and Elm1 protein kinase-dependent manner. As the timing of the initiation of Ca(2+)-induced expression of GPX1 was retarded in an snf1Delta mutant, the activation of Snf1 seems pivotal to the early-stage-response of GPX1 to Ca(2+).

摘要

酿酒酵母有三个谷胱甘肽过氧化物酶基因(GPX1、GPX2 和 GPX3)的同源物。我们之前曾报道过,GPX3 的表达是组成型的,而 GPX2 的表达则受到氧化应激和 CaCl2 的诱导,并揭示了涉及的调节机制。在这里,我们表明 GPX1 的表达受葡萄糖饥饿和 CaCl2 处理诱导。GPX1 表达对葡萄糖饥饿和 Ca2+的诱导依赖于转录因子 Msn2 和 Msn4 以及 GPX1 启动子中的顺式作用元件[应激反应元件(STRE)]。Ras/cAMP 途径也参与了 GPX1 的表达。我们发现,Ser/Thr 蛋白激酶 Snf1 参与了葡萄糖饥饿和 Ca2+诱导的 GPX1 表达。Snf1 的激活伴随着 Thr210 的磷酸化。我们发现,Ca2+处理以及葡萄糖饥饿以 Tos3、Sak1 和 Elm1 蛋白激酶依赖的方式引起 Snf1 的 Thr210 磷酸化。由于 Ca2+诱导的 GPX1 表达的起始时间在 snf1Δ突变体中延迟,因此 Snf1 的激活似乎对 GPX1 对 Ca2+的早期反应至关重要。

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