Ubiquitin modifications.
Ubiquitin modifications.
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DOI：
10.1038/cr.2016.39
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发表时间：
2016-04
期刊：
影响因子：
44.1
通讯作者：
Komander D
中科院分区：
文献类型：
--
作者：
Swatek KN;Komander D
蛋白质泛素化是一种动态的多方面的翻译后修饰，涉及到真核生物学的几乎所有方面。一旦连接到底物上，76个氨基酸的蛋白质泛蛋白就会受到进一步的修饰，产生大量具有不同细胞结果的不同信号，称为“泛蛋白密码”。泛素可以在7个赖氨酸（Lys）残基或N-末端上被泛素化，导致可以包含复杂拓扑结构的多聚泛素链。可替代地或另外地，泛素Lys残基可以被泛素样分子（诸如SUMO或NEDD 8）修饰。最后，泛素还可以在Lys上乙酰化，或在Ser、Thr或Tyr残基上磷酸化，并且每种修饰都有可能显著改变信号传导结果。虽然细胞中明显修饰的泛素种类的数量令人难以置信，但在表征不同泛素修饰的作用方面已经取得了很大进展，并且已经鉴定了许多酶和受体，它们可以产生，识别或去除这些泛素修饰。我们在这里提供了一个概述的各种泛素修饰存在于细胞中，并强调泛素链生物学的最新进展。然后，我们讨论了泛素乙酰化和磷酸化领域的最新研究结果，重点是Ser 65-磷酸化及其在线粒体自噬和帕金激活中的作用。
Protein ubiquitination is a dynamic multifaceted post-translational modification involved in nearly all aspects of eukaryotic biology. Once attached to a substrate, the 76-amino acid protein ubiquitin is subjected to further modifications, creating a multitude of distinct signals with distinct cellular outcomes, referred to as the 'ubiquitin code'. Ubiquitin can be ubiquitinated on seven lysine (Lys) residues or on the N-terminus, leading to polyubiquitin chains that can encompass complex topologies. Alternatively or in addition, ubiquitin Lys residues can be modified by ubiquitin-like molecules (such as SUMO or NEDD8). Finally, ubiquitin can also be acetylated on Lys, or phosphorylated on Ser, Thr or Tyr residues, and each modification has the potential to dramatically alter the signaling outcome. While the number of distinctly modified ubiquitin species in cells is mind-boggling, much progress has been made to characterize the roles of distinct ubiquitin modifications, and many enzymes and receptors have been identified that create, recognize or remove these ubiquitin modifications. We here provide an overview of the various ubiquitin modifications present in cells, and highlight recent progress on ubiquitin chain biology. We then discuss the recent findings in the field of ubiquitin acetylation and phosphorylation, with a focus on Ser65-phosphorylation and its role in mitophagy and Parkin activation.