Rodríguez-Gabriel Miguel A, Burns Gavin, McDonald W Hayes, Martín Victoria, Yates John R, Bähler Jürg, Russell Paul
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
EMBO J. 2003 Dec 1;22(23):6256-66. doi: 10.1093/emboj/cdg597.
Fission yeast Spc1 (Sty1), a stress-activated mitogen-activated protein kinase (MAPK) homologous to human p38, orchestrates global changes in gene expression in response to diverse forms of cytotoxic stress. This control is partly mediated through Atf1, a transcription factor homologous to human ATF2. How Spc1 controls Atf1, and how the cells tailor gene expression patterns to different forms of stress, are unknown. Here we describe Csx1, a novel protein crucial for survival of oxidative but not osmotic stress. Csx1 associates with and stabilizes atf1+ mRNA in response to oxidative stress. Csx1 controls expression of the majority of the genes induced by oxidative stress, including most of the genes regulated by Spc1 and Atf1. These studies reveal a novel mechanism controlling MAPK-regulated transcription factors and suggest how gene expression patterns can be customized to specific forms of stress. Csx1-like proteins in humans may perform similar tasks.
裂殖酵母Spc1(Sty1)是一种与人类p38同源的应激激活丝裂原活化蛋白激酶(MAPK),它能协调基因表达的全局变化以应对多种形式的细胞毒性应激。这种调控部分是通过Atf1介导的,Atf1是一种与人类ATF2同源的转录因子。Spc1如何控制Atf1,以及细胞如何根据不同形式的应激调整基因表达模式,目前尚不清楚。在这里,我们描述了Csx1,一种对氧化应激而非渗透应激的存活至关重要的新型蛋白质。Csx1在氧化应激反应中与atf1+ mRNA结合并使其稳定。Csx1控制着氧化应激诱导的大多数基因的表达,包括大多数受Spc1和Atf1调控的基因。这些研究揭示了一种控制MAPK调节转录因子的新机制,并提出了如何根据特定形式的应激定制基因表达模式。人类中的Csx1样蛋白可能执行类似的任务。