Small GTP-binding protein Ran is regulated by posttranslational lysine acetylation
Small GTP-binding protein Ran is regulated by posttranslational lysine acetylation
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DOI：
10.1073/pnas.1505995112
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发表时间：
2015-07-14
影响因子：
11.1
通讯作者：
Lammers, Michael
中科院分区：
文献类型：
--
作者：
de Boor, Susanne;Knyphausen, Philipp;Lammers, Michael
Ran是Ras超家族的一种小的GTP结合蛋白，调节基本的细胞过程：核质转运、核膜形成和有丝分裂纺锤体组装。由其调节剂RCC 1和RanGAP的不同亚细胞定位产生的细胞内Ran.GTP/Ran.GDP梯度介导其许多细胞效应。最近的蛋白质组学筛选确定了5个Ran赖氨酸乙酰化位点在人类和11个网站在小鼠/大鼠组织。其中一些站点位于功能非常重要的区域，例如开关I和开关II。在这里，我们表明，赖氨酸乙酰化干扰RAN功能的基本方面：核苷酸交换和水解，亚细胞RAN本地化，GTP水解，以及与进出口受体的相互作用。在体外检测了某些sirtuins的两个Ran乙酰化位点的脱乙酰化活性。此外，Ran在体外被CBP/p300和Tip 60乙酰化，并在体内过表达转移酶。总的来说，这项研究解决了许多重要的挑战，乙酰基领域，这将被讨论。
Ran is a small GTP-binding protein of the Ras superfamily regulating fundamental cellular processes: nucleo-cytoplasmic transport, nuclear envelope formation and mitotic spindle assembly. An intracellular Ran.GTP/Ran.GDP gradient created by the distinct subcellular localization of its regulators RCC1 and RanGAP mediates many of its cellular effects. Recent proteomic screens identified five Ran lysine acetylation sites in human and eleven sites inmouse/rat tissues. Some of these sites are located in functionally highly important regions such as switch I and switch II. Here, we show that lysine acetylation interferes with essential aspects of Ran function: nucleotide exchange and hydrolysis, subcellular Ran localization, GTP hydrolysis, and the interaction with import and export receptors. Deacetylation activity of certain sirtuins was detected for two Ran acetylation sites in vitro. Moreover, Ran was acetylated by CBP/p300 and Tip60 in vitro and on transferase overexpression in vivo. Overall, this study addresses many important challenges of the acetylome field, which will be discussed.