CEA, iBiTecS, SBIGeM, Bât 144, F-91191 Gif sur Yvette, France.
Semin Cell Dev Biol. 2012 Jul;23(5):538-45. doi: 10.1016/j.semcdb.2012.02.004. Epub 2012 Feb 14.
DNA damage is a major threat to genome integrity. To reduce its deleterious effects, cells have developed coordinated responses, collectively referred to as the "DNA damage response" pathway (DDR). In multicellular organisms, the DDR pathway has a critical role in preventing tumorigenesis, which accounts for the wide use of drugs targeting DDR factors in anti-cancer therapy. Post-translational modifications such as phosphorylation, ubiquitylation, acetylation, sumoylation are integral part of the DDR pathway. Ubiquitylation of DDR-related factors has recently emerged both as a switch initiating signaling cascades and as a proteolytic signal coordinating recruitment and disassembly of those proteins. In this review we will present evidence supporting an increasingly important role for the ubiquitin-proteasome-mediated degradation in regulating DDR at different levels.
DNA 损伤是基因组完整性的主要威胁。为了减少其有害影响，细胞已经发展出协调的反应，统称为“DNA 损伤反应”途径（DDR）。在多细胞生物中，DDR 途径在预防肿瘤发生方面起着关键作用，这也是靶向 DDR 因子的药物在癌症治疗中广泛应用的原因。翻译后的修饰，如磷酸化、泛素化、乙酰化、SUMO 化，是 DDR 途径的组成部分。DDR 相关因子的泛素化最近不仅作为启动信号级联的开关，而且作为协调这些蛋白质招募和拆卸的蛋白水解信号出现。在这篇综述中，我们将提出支持泛素-蛋白酶体介导的降解在不同水平上调节 DDR 的作用越来越重要的证据。
