Ohtake Fumiaki, Saeki Yasushi, Sakamoto Kensaku, Ohtake Kazumasa, Nishikawa Hiroyuki, Tsuchiya Hikaru, Ohta Tomohiko, Tanaka Keiji, Kanno Jun
Division of Cellular and Molecular Toxicology, Biological Safety Research Center, National Institute of Health Sciences, Setagaya-ku Tokyo, Japan
Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Sciences, Setagaya-ku Tokyo, Japan.
EMBO Rep. 2015 Feb;16(2):192-201. doi: 10.15252/embr.201439152. Epub 2014 Dec 19.
Ubiquitylation is a versatile post-translational modification (PTM). The diversity of ubiquitylation topologies, which encompasses different chain lengths and linkages, underlies its widespread cellular roles. Here, we show that endogenous ubiquitin is acetylated at lysine (K)-6 (AcK6) or K48. Acetylated ubiquitin does not affect substrate monoubiquitylation, but inhibits K11-, K48-, and K63-linked polyubiquitin chain elongation by several E2 enzymes in vitro. In cells, AcK6-mimetic ubiquitin stabilizes the monoubiquitylation of histone H2B-which we identify as an endogenous substrate of acetylated ubiquitin-and of artificial ubiquitin fusion degradation substrates. These results characterize a mechanism whereby ubiquitin, itself a PTM, is subject to another PTM to modulate mono- and polyubiquitylation, thus adding a new regulatory layer to ubiquitin biology.
泛素化是一种多功能的翻译后修饰（PTM）。泛素化拓扑结构的多样性，包括不同的链长和连接方式，是其在细胞中广泛作用的基础。在这里，我们表明内源性泛素在赖氨酸（K）-6（AcK6）或K48处被乙酰化。乙酰化泛素不影响底物单泛素化，但在体外抑制几种E2酶介导的K11-、K48-和K63连接的多聚泛素链延伸。在细胞中，模拟AcK6的泛素稳定了组蛋白H2B的单泛素化——我们将其鉴定为乙酰化泛素的内源性底物——以及人工泛素融合降解底物的单泛素化。这些结果揭示了一种机制，即泛素本身作为一种翻译后修饰，会受到另一种翻译后修饰的作用来调节单泛素化和多聚泛素化，从而为泛素生物学增添了一个新的调控层面。
