There's the Rub: a novel ubiquitin-like modification linked to cell cycle regulation
There's the Rub: a novel ubiquitin-like modification linked to cell cycle regulation
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DOI：
10.1101/gad.12.7.901
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发表时间：
1998-04-01
影响因子：
10.5
通讯作者：
Hochstrasser, M
中科院分区：
文献类型：
--
作者：
Hochstrasser, M
多肽遍在蛋白与细胞内蛋白质的共价连接是通过一种复杂且高度保守的酶途径实现的，该途径已开始被详细了解（有关综述，请参见威尔金森1995; Hochstrasser 1996; Pickart 1997）。泛素通过泛素羧基端羧基与受体蛋白赖氨酸侧链的异肽键可逆地连接到蛋白质上（图1）。在大多数检查的情况下，修饰的蛋白质，特别是当它连接到多个泛素分子时，靶向一种称为蛋白酶体的大的、丰富的细胞内蛋白酶，其将底物降解成小肽，但允许泛素部分的再循环。已经发现真核生物也表达一组泛素样蛋白（Ubls），它们与泛素本身显著不同，但也与其他蛋白连接（哈斯和Siepmann 1997;约翰逊和Hochstrasser 1997）。涉及这些变体的反应似乎与泛素的反应有很多共同之处，但Ubls具有新的调节功能，不一定与蛋白水解有关。在这个问题上，Lammer等人描述了一个意想不到的联系之间的Ubl称为Rub 1（相关的泛素1）从酵母酿酒酵母和泛素蛋白连接酶复合物，这是关键的进展从G1期到S期的细胞周期。在这篇评论中，我将讨论这些新的结果连同最近的相关发展的机制和功能的Ubl蛋白连接。
Covalent attachment of the polypeptide ubiquitin to intracellular proteins is achieved through an intricate and highly conserved enzymatic pathway that is beginning to be understood in some detail (for review, see Wilkinson 1995; Hochstrasser 1996; Pickart 1997). Ubiquitin is joined reversibly to proteins by an isopeptide linkage of the carboxy-terminal carboxyl group of ubiquitin to lysine side chains of the acceptor proteins (Fig. 1). In the majority of cases examined, the modified protein, particularly when it is attached to multiple ubiquitin molecules, is targeted to a large, abundant intracellular protease called the proteasome, which degrades the substrate into small peptides but allows recycling of the ubiquitin moieties.Over the past few years, it has emerged that eukaryotes also express a set of ubiquitin-like proteins (Ubls) that are significantly diverged from ubiquitin itself yet are also ligated to other proteins (Haas and Siepmann 1997; Johnson and Hochstrasser 1997). The reactions involving these variants appear to have much in common with those of ubiquitin, but the Ubls have novel regulatory functions not necessarily linked to proteolysis. In this issue, Lammer et al. describe an unexpected connection between a Ubl called Rub1 (related to ubiquitin 1) from the yeast Saccharomyces cerevisiae and a ubiquitin–protein ligase complex that is critical for progression from G1 to S phase in the cell cycle. In this commentary, I will discuss these new results together with recent related developments on the mechanisms and functions of Ubl–protein ligation.