PDF(Pubmed)
Abstract：
Ferroptosis is a form of iron-related oxidative cell death governed by an integrated redox system, encompassing pro-oxidative proteins and antioxidative proteins. These proteins undergo precise control through diverse post-translational modifications, including ubiquitination, phosphorylation, acetylation, O-GlcNAcylation, SUMOylation, methylation, N-myristoylation, palmitoylation, and oxidative modification. These modifications play pivotal roles in regulating protein stability, activity, localization, and interactions, ultimately influencing both the buildup of iron and lipid peroxidation. In mammalian cells, regulators of ferroptosis typically undergo degradation via two principal pathways: the ubiquitin-proteasome system, which handles the majority of protein degradation, and autophagy, primarily targeting long-lived or aggregated proteins. This comprehensive review aims to summarize recent advances in the post-translational modification and degradation of proteins linked to ferroptosis. It also discusses strategies for modulating ferroptosis through protein modification and degradation systems, providing new insights into potential therapeutic applications for both cancer and non-neoplastic diseases.
摘要：
Ferroptosis是一种与铁相关的氧化性细胞死亡，由一个完整的氧化还原系统控制。包括促氧化蛋白和抗氧化蛋白。这些蛋白质通过不同的翻译后修饰进行精确控制，包括泛素化，磷酸化,乙酰化,O-GlcNAcylation,SUMOylation,甲基化,N-肉豆蔻酰化,棕榈酰化，和氧化改性。这些修饰在调节蛋白质的稳定性中起着关键作用。活动,本地化,和互动，最终影响铁和脂质过氧化的积累。在哺乳动物细胞中,铁凋亡的调节因子通常通过两个主要途径进行降解：泛素-蛋白酶体系统，处理大部分蛋白质降解，和自噬,主要针对长寿命或聚集蛋白质。这篇综合综述旨在总结与铁凋亡相关的蛋白质的翻译后修饰和降解的最新进展。它还讨论了通过蛋白质修饰和降解系统调节铁死亡的策略，为癌症和非肿瘤性疾病的潜在治疗应用提供新的见解。
