Araki Yoshio, Wu Hong, Kitagaki Hiroshi, Akao Takeshi, Takagi Hiroshi, Shimoi Hitoshi
National Research Institute of Brewing, 3-7-1, Kagamiyama, Higashihiroshima 739-0046, Japan.
J Biosci Bioeng. 2009 Jan;107(1):1-6. doi: 10.1016/j.jbiosc.2008.09.005.
Environmental stimuli elicit a stress response, which helps to maintain cell survival. In budding yeast Saccharomyces cerevisiae, environmental cues can activate calcineurin, a highly conserved Ca2+-- and calmodulin-dependent protein phosphatase. Calcineurin dephosphorylates the transcription factor Crz1, leading to accumulation of Crz1 in the nuclei and expression of stress responsive genes under the control of a calcineurin-dependent response element (CDRE). Ethanol is the final product of sugar fermentation by yeast, and thus a frequently encountered yeast stressor. However, adaptation of yeast to ethanol stress is poorly understood. In this study, we show that ethanol stimulates calcineurin-dependent nuclear localization of Crz1 and CDRE-dependent gene expression. Moreover, cells in which CRZ1 is deleted exhibit defective adaptation to ethanol stress, while a multicopy plasmid of CRZ1 confers an increased level of adaptive stress tolerance to ethanol. Taken together, the results indicate that ethanol activates the calcineurin/Crz1 pathway and that CRZ1 is crucial for cell survival under ethanol-induced stress.
环境刺激引发应激反应，这有助于维持细胞存活。在芽殖酵母酿酒酵母中，环境信号可激活钙调神经磷酸酶，这是一种高度保守的钙和钙调蛋白依赖性蛋白磷酸酶。钙调神经磷酸酶使转录因子Crz1去磷酸化，导致Crz1在细胞核中积累，并在钙调神经磷酸酶依赖性反应元件（CDRE）的控制下表达应激反应基因。乙醇是酵母糖发酵的最终产物，因此是酵母经常遇到的应激源。然而，酵母对乙醇应激的适应性却知之甚少。在本研究中，我们表明乙醇刺激Crz1的钙调神经磷酸酶依赖性核定位和CDRE依赖性基因表达。此外，缺失CRZ1的细胞对乙醇应激的适应性存在缺陷，而CRZ1的多拷贝质粒赋予细胞对乙醇的适应性应激耐受性增加。综上所述，结果表明乙醇激活钙调神经磷酸酶/Crz1途径，并且CRZ1对于乙醇诱导的应激下的细胞存活至关重要。
