Ubiquitin acetylation inhibits polyubiquitin chain elongation
Ubiquitin acetylation inhibits polyubiquitin chain elongation
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DOI：
10.15252/embr.201439152
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发表时间：
2015-02-01
期刊：
影响因子：
7.7
通讯作者：
Kanno, Jun
中科院分区：
文献类型：
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作者：
Ohtake, Fumiaki;Saeki, Yasushi;Kanno, Jun
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，包括不同的链长度和连接，奠定了其广泛的细胞作用。在这里，我们发现内源性泛素在赖氨酸(K)-6 （AcK6）或K48位点乙酰化。乙酰化泛素不影响底物单泛素化，但通过几种E2酶在体外抑制K11-、K48-和k63 -连接的多泛素链延伸。在细胞中，ack6模拟泛素稳定了组蛋白h2b的单泛素化，我们认为h2b是乙酰化泛素的内源性底物，也是人工泛素融合降解底物。这些结果表征了一种机制，即泛素本身是一种PTM，受另一种PTM调节单泛素化和多泛素化，从而为泛素生物学增加了一个新的调控层。
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.