Ruth Children Hospital, Rambam Health Campus, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Technion Integrated Cancer Center (TICC), Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
J Allergy Clin Immunol. 2017 Mar;139(3):743-753. doi: 10.1016/j.jaci.2016.11.031.
The importance of the ubiquitin system in health and disease has been widely recognized in recent decades, with better understanding of the various components of the system and their function. Ubiquitination, which is essential to almost all biological processes in eukaryotes, was also found to play an important role in innate and adaptive immune responses. Thus it is not surprising that mutations in genes coding for components of the ubiquitin system cause immune dysregulation. The first defect in the system was described 30 years ago and is due to mutations in the nuclear factor κB (NF-κB) essential modulator, a key regulator of the NF-κB pathway. With use of novel sequencing techniques, many additional mutations in different genes involved in ubiquitination and related to immune system function were identified. This can be clearly illustrated in mutations in the different activation pathways of NF-κB, which result in aberrations in production of various proinflammatory cytokines. The inherited diseases typically manifest with immunodeficiency, autoimmunity, or autoinflammation. In this perspective we provide a short description of the ubiquitin system, with specific emphasis given to its role in the immune system. The various immunodeficiency conditions identified thus far in association with defective ubiquitination are discussed in more detail.
近年来，泛素系统在健康和疾病中的重要性已得到广泛认可，人们对该系统的各个组成部分及其功能有了更好的理解。泛素化对于真核生物的几乎所有生物过程都是必不可少的，它在先天和适应性免疫反应中也起着重要作用。因此，编码泛素系统成分的基因突变会导致免疫失调也就不足为奇了。该系统的第一个缺陷是在 30 年前描述的，其原因是核因子 κB（NF-κB）必需调节剂的基因突变，NF-κB 途径的关键调节剂。随着新型测序技术的应用，发现了许多与免疫系统功能相关的不同基因参与泛素化的其他突变。这在 NF-κB 的不同激活途径中的突变中可以清楚地说明，这些突变导致各种促炎细胞因子的产生异常。这些遗传性疾病通常表现为免疫缺陷、自身免疫或自身炎症。在这一观点中，我们简要描述了泛素系统，特别强调了它在免疫系统中的作用。目前已确定的与泛素化缺陷相关的各种免疫缺陷情况将进行更详细的讨论。
