SUMOylation of the nuclear pore complex basket is involved in sensing cellular stresses

SUMOylation of the nuclear pore complex basket is involved in sensing cellular stresses
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DOI:
10.1242/jcs.224279
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发表时间:
2019-04-01
影响因子:
4
通讯作者:
Dargemont, Catherine
Dargemont, Catherine
中科院分区:
生物学2区
文献类型:
--
作者:
Folz, Hanne;Nino, Carlos A.;Dargemont, Catherine

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核孔复合体(NPC)是核质运输的主要通道,是基因调控和DNA修复的平台。一些核孔蛋白经历泛素化和SUMO化,这些修饰在核孔动力学和可塑性中起着重要的作用。在这里,我们对酵母核篮子蛋白在正常生长条件下以及在细胞压力下的这些翻译后修饰进行了详细的分析,重点是SUMO化。我们发现在鼻咽癌中,Nup60和Nup2的SUMO化和去SUMO之间的动态平衡有很大的不同,特别是在G1期和S期。虽然Nup60是核篮子中基因毒性应激的唯一靶点,可能属于相扑介导的DNA损伤反应途径,但Nup2和Nup60都显示在渗透胁迫下SUMO化显著增加,在Nup60缺失突变酵母菌株中,Nup2 SUMO化增强。综上所述,我们的数据揭示了核孔蛋白之间存在几个水平的串扰,并且NPC的翻译后修饰在感知细胞应激信号方面起到了作用。
The nuclear pore complex (NPC) is the major conduit for nucleocytoplasmic transport and serves as a platform for gene regulation and DNA repair. Several nucleoporins undergo ubiquitylation and SUMOylation, and these modifications play an important role in nuclear pore dynamics and plasticity. Here, we perform a detailed analysis of these post-translational modifications of yeast nuclear basket proteins under normal growth conditions as well as upon cellular stresses, with a focus on SUMOylation. We find that the balance between the dynamics of SUMOylation and deSUMOylation of Nup60 and Nup2 at the NPC differs substantially, particularly in G1 and S phase. While Nup60 is the unique target of genotoxic stress within the nuclear basket that probably belongs to the SUMO-mediated DNA damage response pathway, both Nup2 and Nup60 show a dramatic increase in SUMOylation upon osmotic stress, with Nup2 SUMOylation being enhanced in Nup60 SUMO-deficient mutant yeast strains. Taken together, our data reveal that there are several levels of crosstalk between nucleoporins, and that the post-translational modifications of the NPC serve in sensing cellular stress signals.