Forkhead box, class O (FOXO) family proteins are widely expressed and highly conserved transcriptional regulators that modulate cellular fuel metabolism, stress resistance and cell death. FOXO target genes include genes encoding antioxidant proteins, thus likely contributing to the key role FOXOs play in the cellular response to oxidative stress and supporting the cellular strategies of antioxidant defense, that is, prevention (of the formation of reactive oxygen species), interception (of reactive species prior to their reaction with cellular components), repair (of damaged biomolecules), and adaptation (i.e., the stimulation of signaling pathways allowing for the expression of protective proteins). FOXOs themselves are regulated by redox processes at several levels, including expression of FOXO genes and enzymatic as well as nonenzymatic posttranslational modifications of FOXO proteins. The latter include modifications of FOXO cysteine residues. Here, an overview is provided on (i) the contribution of FOXO target genes to cellular antioxidative strategies, and (ii) on the impact of thiol homeostasis and thiol modification on FOXO activity.

中文翻译：

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抗氧化防御中的 FOXO 转录因子

Forkhead box，O 类 (FOXO) 家族蛋白是广泛表达且高度保守的转录调节因子，可调节细胞燃料代谢、抗应激和细胞死亡。FOXO 靶基因包括编码抗氧化蛋白的基因，因此可能有助于 FOXO 在细胞对氧化应激的反应中发挥关键作用，并支持抗氧化防御的细胞策略，即预防（活性氧的形成）、拦截（与细胞成分反应之前的活性物质）、修复（受损的生物分子）和适应（即刺激信号通路允许保护性蛋白质的表达）。FOXO 本身受多个水平的氧化还原过程的调节，包括FOXO的表达基因和 FOXO 蛋白的酶促和非酶促翻译后修饰。后者包括 FOXO 半胱氨酸残基的修饰。在这里，概述了 (i) FOXO 靶基因对细胞抗氧化策略的贡献，以及 (ii) 硫醇稳态和硫醇修饰对 FOXO 活性的影响。