ABSTRACT

Post-translational modifications (PTMs) are critical drivers and attenuators for proteins that regulate immune signalling cascades in host defence. In this review, we explore functional roles for one such PTM, the small ubiquitin-like modifier (SUMO). Very few of the SUMO conjugation targets identified by proteomic studies have been validated in terms of their roles in host defence. Here, we compare and contrast potential SUMO substrate proteins in immune signalling for flies and mammals, with an emphasis on NFκB pathways. We discuss, using the few mechanistic studies that exist for validated targets, the effect of SUMO conjugation on signalling and also explore current molecular models that explain regulation by SUMO. We also discuss in detail roles of evolutionary conservation of mechanisms, SUMO interaction motifs, crosstalk of SUMO with other PTMs, emerging concepts such as group SUMOylation and finally, the potentially transforming roles for genome-editing technologies in studying the effect of PTMs.

 抽象的

翻译后修饰 (PTM) 是调节宿主防御中免疫信号级联的蛋白质的关键驱动因素和衰减因素。在这篇综述中，我们探讨了这样一种 PTM，即小泛素样修饰剂 (SUMO) 的功能作用。蛋白质组学研究确定的 SUMO 结合靶标很少在宿主防御中的作用得到验证。在这里，我们比较和对比果蝇和哺乳动物免疫信号中潜在的 SUMO 底物蛋白，重点是 NFκB 通路。我们利用针对已验证靶标存在的少数机制研究，讨论了 SUMO 缀合对信号传导的影响，并探索了解释 SUMO 调节的当前分子模型。我们还详细讨论了机制进化保守性、SUMO 相互作用基序、SUMO 与其他 PTM 的串扰、群体 SUMO 化等新兴概念，以及基因组编辑技术在研究 PTM 效果中的潜在转变作用。