Discovery of linear ubiquitination, a crucial regulator for immune signaling and cell death,The FEBS Journal

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Discovery of linear ubiquitination, a crucial regulator for immune signaling and cell death
The FEBS Journal ( IF 5.5 ) Pub Date : 2020-07-05 , DOI: 10.1111/febs.15471
Kazuhiro Iwai ₁

Affiliation

Ubiquitination is a reversible post‐translational modification that regulates function of conjugated proteins by decorating with ubiquitin chains—polymer of ubiquitin—in most cases. The discovery of linear ubiquitin chains and the linear ubiquitin chain assembly complex (LUBAC) ubiquitin ligase complex can be considered as paradigm shift in the ubiquitin research because the linear ubiquitin chain is generated via the N‐terminal Met of ubiquitin, although the other ubiquitin chains are generated via one of seven Lys residues in ubiquitin. Moreover, ubiquitination is distributed throughout eukaryotic kingdoms; however, no linear ubiquitination could be found in lower eukaryotes including yeasts. Although the involvement of ubiquitination in proteolysis is well‐documented, linear ubiquitination plays crucial roles in immune signaling and cell death regulation. Moreover, dysregulation of LUBAC‐mediated linear ubiquitination underlies various human diseases including autoinflammation and cancer. Here, I introduce how linear ubiquitination was discovered and outline a brief history of linear ubiquitination research.

中文翻译：

线性泛素化的发现，线性泛素化是免疫信号和细胞死亡的关键调节剂

泛素化是一种可逆的翻译后修饰，在大多数情况下通过修饰泛素链（泛素的聚合物）来调节结合蛋白的功能。线性泛素链和线性泛素链组装复合体（LUBAC）泛素连接酶复合体的发现可被视为泛素研究的范式转变，因为线性泛素链是通过泛素的N末端Met生成的，尽管其他泛素链是通过遍在蛋白中的七个Lys残基之一产生。此外，泛素化分布在整个真核王国中。然而，在包括酵母在内的低等真核生物中未发现线性泛素化。尽管泛素化参与了蛋白水解的研究有据可查，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。此外，LUBAC介导的线性泛素化失调是各种人类疾病的基础，包括自身炎症和癌症。在这里，我将介绍如何发现线性泛素化并概述线性泛素化研究的简要历史。

更新日期：2020-07-05

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