Protein monoubiquitylation: targets and diverse functions.
Protein monoubiquitylation: targets and diverse functions.
复制标题
DOI：
10.1111/gtc.12250
复制
发表时间：
2015-07
期刊：
影响因子：
--
通讯作者：
Nakayama K
中科院分区：
文献类型：
--
作者：
Nakagawa T;Nakayama K
泛素是一种 76 个氨基酸的蛋白质，其与蛋白质靶标的缀合是翻译后修饰的一种形式。蛋白质泛素化的特征是泛素的COOH末端羧基与底物蛋白的氨基共价连接。鉴于 NH2 末端氨基通常被掩蔽，内部赖氨酸残基最常成为泛素化的目标。多聚泛素化是指由于缀合泛素泛素化而在底物上形成多聚泛素链。这种多聚泛素链的结构取决于泛素泛素化的特定赖氨酸残基。除通过泛素赖氨酸-63 和蛋氨酸-1 连接的链外，大多数多聚泛素链均被蛋白酶体识别，并作为底物降解的触发因素。相比之下，通过赖氨酸-63 和蛋氨酸-1 连接的多聚泛素链充当在免疫信号转导或 DNA 修复中发挥作用的蛋白质的结合平台。除了组蛋白等少数靶标外，蛋白质单泛素化的功能仍不太清楚。然而，最近的蛋白质组学分析表明，单泛素化比多泛素化发生的频率更高，并且研究开始深入了解其重要的生物学功能。在这里，我们总结了蛋白质单泛素化的最新发现，以概述这种修饰的靶点和分子功能。
Ubiquitin is a 76‐amino acid protein whose conjugation to protein targets is a form of post‐translational modification. Protein ubiquitylation is characterized by the covalent attachment of the COOH‐terminal carboxyl group of ubiquitin to an amino group of the substrate protein. Given that the NH2‐terminal amino group is usually masked, internal lysine residues are most often targeted for ubiquitylation. Polyubiquitylation refers to the formation of a polyubiquitin chain on the substrate as a result of the ubiquitylation of conjugated ubiquitin. The structures of such polyubiquitin chains depend on the specific lysine residues of ubiquitin targeted for ubiquitylation. Most of the polyubiquitin chains other than those linked via lysine‐63 and methionine‐1 of ubiquitin are recognized by the proteasome and serve as a trigger for substrate degradation. In contrast, polyubiquitin chains linked via lysine‐63 and methionine‐1 serve as a binding platform for proteins that function in immune signal transduction or DNA repair. With the exception of a few targets such as histones, the functions of protein monoubiquitylation have remained less clear. However, recent proteomics analysis has shown that monoubiquitylation occurs more frequently than polyubiquitylation, and studies are beginning to provide insight into its biologically important functions. Here, we summarize recent findings on protein monoubiquitylation to provide an overview of the targets and molecular functions of this modification.