Asr1p, a novel yeast RNA Polymerase II CTD-binding protein signals alcohol stress to the nucleus

细胞将不利的条件感知为潜在的压力，将其传达给细胞核，并通过改变转录活性对其做出反应。面包酵母S.酿酒酵母作为一个简单的模式生物，分析信号转导和基因表达调控响应酒精胁迫。酒精对细胞的生理机能有多种作用。首先，酒精会改变膜结构并使蛋白质变性。为了补偿发酵过程中发生的这种应激情况，酵母细胞以改变的转录活性做出反应。我们已经确定了面包酵母的一种新蛋白质，这种蛋白质在酒精存在的情况下是重要生长所需的，因此也是修复或适应过程所需的。Asr 1 p（Alcohol sensitive RING/PHD finger 1 protein）在细胞质和细胞核之间组成性穿梭，但在酒精胁迫时在细胞核中积累。Asr 1 p对酒精有特异性和可逆性反应，但对饥饿、热、渗透压或氧化应激无反应。与特异性转录因子相反，Asr 1 p不结合启动子区域，而是靶向RNA聚合酶II的最大亚基Rpb 1 p的C-末端结构域（CTD），该结构域对于转录活性的调节和整合至关重要。由于Asr 1 p是第一个被报道的在酒精胁迫下特异性改变其亚细胞定位的酵母蛋白，因此它提供了解开酒精胁迫期间酒精诱导的信号传导事件和转录调控的关键。

Cells sense unfavorable conditions as potentially stressful, communicate it among other things to the nucleus and respond to it by altered transcriptional activity. The baker¿s yeast S. cerevisiae serves as a simple model organism to analyse signal transduction and regulation of gene expression in response to alcohol stress. Alcohol has pleiotropic effects on the physiology of the cell. Primarily, alcohol alters the membrane structure and denatures proteins. To compensate this stressful situation that occurs during fermentation, yeast cells respond with altered transcriptional activity. We have identified a novel protein of baker¿s yeast required for vital growth in presence of alcohol and thus for repair or adaptation processes. Asr1p (Alcohol sensitive RING/PHD finger 1 protein) constitutively shuttles between cytoplasm and nucleus but accumulates in the nucleus upon alcohol stress. Asr1p responds specifically and reversibly to alcohol but not to starvation, heat, osmotic or oxidative stress. In contrast to specific transcription factors, Asr1p does not bind to promoter regions but targets the C-terminal domain (CTD) of the largest subunit Rpb1p of RNA-Polymerase II, a domain crucial for regulation and integration of transcriptional activities. Since Asr1p is the first yeast protein reported that changes its subcellular localization specifically upon alcohol stress, it provides a key to unravel alcohol induced signaling events and transcriptional regulation during alcohol stress.