Morgan B A, Banks G R, Toone W M, Raitt D, Kuge S, Johnston L H
Department of Biochemistry and Genetics, Medical School, University of Newcastle, Newcastle-upon-Tyne, UK.
EMBO J. 1997 Mar 3;16(5):1035-44. doi: 10.1093/emboj/16.5.1035.
Deletion of the bacterial two-component response regulator homologue Skn7 results in sensitivity of yeast to oxidizing agents indicating that Skn7 is involved in the response to this type of stress. Here we demonstrate that following oxidative stress, Skn7 regulates the induction of two genes: TRX2, encoding thioredoxin, and a gene encoding thioredoxin reductase. TRX2 is already known to be induced by oxidative stress dependent on the Yap1 protein, an AP1-like transcription factor responsible for the induction of gene expression in response to various stresses. The thioredoxin reductase gene has not previously been shown to be activated by oxidative stress and, significantly, we find that it too is regulated by Yap1. The control of at least TRX2 by Skn7 is a direct mechanism as Skn7 binds to the TRX2 gene promoter in vitro. This shows Skn7 to be a transcription factor, at present the only such eukaryotic two-component signalling protein. Our data further suggest that Skn7 and Yap1 co-operate on the TRX2 promoter, to induce transcription in response to oxidative stress.
细菌双组分反应调节因子同源物Skn7的缺失导致酵母对氧化剂敏感,这表明Skn7参与了对这类应激的反应。在此我们证明,在氧化应激后,Skn7调节两个基因的诱导:编码硫氧还蛋白的TRX2和一个编码硫氧还蛋白还原酶的基因。已知TRX2在依赖Yap1蛋白的氧化应激诱导下表达,Yap1是一种AP1样转录因子,负责在各种应激反应中诱导基因表达。硫氧还蛋白还原酶基因此前尚未被证明可被氧化应激激活,重要的是,我们发现它也受Yap1调节。Skn7对至少TRX2的调控是一种直接机制,因为Skn7在体外可与TRX2基因启动子结合。这表明Skn7是一种转录因子,目前是唯一的此类真核双组分信号蛋白。我们的数据进一步表明,Skn7和Yap1在TRX2启动子上协同作用,以响应氧化应激诱导转录。