Ubiquitination is a reversible post-translational modification in which ubiquitin chains are conjugated to target proteins to modulate protein function. The type of ubiquitin chain determines the mode of protein regulation. It has been shown that ubiquitin chains are formed via one of seven Lys residues in ubiquitin, and several types of ubiquitin chains are found in cells. We identified a new type of linear ubiquitin chain linked through the N-terminal Met of ubiquitin and assembled by the linear ubiquitin chain assembly complex (LUBAC), which is specific for linear chains. The discovery of linear ubiquitin chains and LUBAC is considered as a paradigm shift in ubiquitin research because linear ubiquitination is exclusive to animals, despite the existence of ubiquitination throughout eukaryotic kingdoms. Linear ubiquitination plays a critical role in immune signaling and cell death regulation. Dysregulation of LUBAC-mediated linear ubiquitination underlies various human diseases, including autoinflammation, autoimmunity, infection, and malignant tumors. This review summarizes the current status of linear ubiquitination research.

泛素化是一种可逆的翻译后修饰，其中泛素链与靶蛋白结合以调节蛋白质功能。泛素链的类型决定了蛋白质调控的方式。已经表明，泛素链是通过泛素中的七个赖氨酸残基之一形成的，并且在细胞中发现了几种类型的泛素链。我们鉴定了一种新型的线性泛素链，通过泛素的 N 端 Met 连接，并由线性泛素链组装复合物 (LUBAC) 组装，该复合物对线性链具有特异性。线性泛素链和 LUBAC 的发现被认为是泛素研究的范式转变，因为线性泛素化是动物独有的，尽管在整个真核生物界都存在泛素化。线性泛素化在免疫信号传导和细胞死亡调节中起关键作用。LUBAC 介导的线性泛素化失调是各种人类疾病的基础，包括自身炎症、自身免疫、感染和恶性肿瘤。本综述总结了线性泛素化研究的现状。