Ubiquitylation is an essential post-translational modification that regulates intracellular signalling networks by triggering proteasomal substrate degradation, changing the activity of substrates or mediating changes in proteins that interact with substrates. Hundreds of enzymes participate in reversible ubiquitylation of proteins, some acting globally and others targeting specific proteins. Ubiquitylation is essential for innate immune responses, as it facilitates rapid regulation of inflammatory pathways, thereby ensuring sufficient but not excessive responses. A growing number of inborn errors of immunity are attributed to dysregulated ubiquitylation. These genetic disorders exhibit broad clinical manifestations, ranging from susceptibility to infection to autoinflammatory and/or autoimmune features, lymphoproliferation and propensity to malignancy. Many autoinflammatory disorders result from disruption of components of the ubiquitylation machinery and lead to overactivation of innate immune cells. An understanding of the disorders of ubiquitylation in autoinflammatory diseases could enable the development of novel management strategies.

泛素化是一种重要的翻译后修饰，它通过触发蛋白酶体底物降解、改变底物的活性或介导与底物相互作用的蛋白质的变化来调节细胞内信号网络。数百种酶参与蛋白质的可逆泛素化，一些在全球范围内发挥作用，另一些则针对特定蛋白质。泛素化对于先天免疫反应至关重要，因为它有助于快速调节炎症通路，从而确保充分但不过度的反应。越来越多的先天性免疫错误归因于失调的泛素化。这些遗传疾病表现出广泛的临床表现，从对感染的易感性到自身炎症和/或自身免疫特征，淋巴组织增生和恶性肿瘤倾向。许多自身炎症性疾病是由泛素化机制的组分破坏引起的，并导致先天免疫细胞过度活化。了解自身炎症性疾病中的泛素化障碍有助于开发新的管理策略。