Wemmie J A, Steggerda S M, Moye-Rowley W S
Department of Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242, USA.
J Biol Chem. 1997 Mar 21;272(12):7908-14. doi: 10.1074/jbc.272.12.7908.
The Saccharomyces cerevisiae AP-1 protein (yAP-1) is a key mediator of oxidative stress tolerance. Transcriptional activation by yAP-1 has been shown to be inducible by exposure of cells to H2O2 and diamide, among other oxidative stress eliciting compounds. Here we define the segments of the yAP-1 protein that are required to respond to this environmental challenge. Western blotting analyses indicated that levels of yAP-1 do not change during oxidative stress. Deletion mutagenesis and gene fusion experiments indicate that two different segments of yAP-1 are required for oxidative stress inducibility. These two domains function differentially depending on the type of oxidant used to generate oxidative stress. Three repeated cysteine-serine-glutamate sequences located in the carboxyl terminus are required for normal regulation of yAP-1 function during oxidative stress. Replacement of these cysteine-serine-glutamate repeats by alanine residues does not similarly affect H2O2 and diamide regulation of yAP-1 function. While yAP-1 transactivation is enhanced by exposure to either H2O2 or diamide, the protein responds to the oxidative stress produced by these compounds in nonidentical ways.
酿酒酵母AP-1蛋白（yAP-1）是氧化应激耐受性的关键介质。yAP-1的转录激活已被证明可通过将细胞暴露于过氧化氢和二酰胺等氧化应激引发化合物来诱导。在这里，我们定义了yAP-1蛋白中应对这种环境挑战所需的片段。蛋白质印迹分析表明，yAP-1的水平在氧化应激期间不会改变。缺失诱变和基因融合实验表明，yAP-1的两个不同片段是氧化应激诱导性所必需的。这两个结构域的功能取决于用于产生氧化应激的氧化剂类型。位于羧基末端的三个重复的半胱氨酸-丝氨酸-谷氨酸序列是氧化应激期间yAP-1功能正常调节所必需的。用丙氨酸残基取代这些半胱氨酸-丝氨酸-谷氨酸重复序列不会类似地影响yAP-1功能的过氧化氢和二酰胺调节。虽然yAP-1的反式激活通过暴露于过氧化氢或二酰胺而增强，但该蛋白以不同的方式响应这些化合物产生的氧化应激。
