Epac1 activation by cAMP regulates cellular SUMOylation and promotes the formation of biomolecular condensates.
Epac1 activation by cAMP regulates cellular SUMOylation and promotes the formation of biomolecular condensates.
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DOI：
10.1126/sciadv.abm2960
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发表时间：
2022-04-22
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
--
作者：
当细胞处于应激状态时，蛋白质SUMOylation在维持细胞稳态中起重要作用。然而，确切地说，SUMOylation是如何调节的，以及将细胞应激与SUMOylation联系起来的分子机制仍然是难以捉摸的。在这里，我们报道了cAMP，一个主要的应激反应第二信使，通过Epac1作为细胞sumo酰化的调节剂。epac1相关的蛋白质组富含sumo化途径的成分。细胞内cAMP激活Epac1可触发相分离，并形成含有Epac1和SUMOylation机制一般组分的核凝聚物，从而促进细胞SUMOylation。此外，基因敲除Epac1可以消除巨噬细胞中氧化的低密度脂蛋白诱导的细胞sumo酰化，从而抑制泡沫细胞的形成。这些结果提供了两个主要的细胞应激反应之间的直接联系，以确定cAMP调节细胞凝聚物动力学以调节蛋白质sumo化的分子机制。应激摔跤与SUMO: camp诱导的Epac1核凝聚加速细胞SUMO化。
Protein SUMOylation plays an essential role in maintaining cellular homeostasis when cells are under stress. However, precisely how SUMOylation is regulated, and a molecular mechanism linking cellular stress to SUMOylation, remains elusive. Here, we report that cAMP, a major stress-response second messenger, acts through Epac1 as a regulator of cellular SUMOylation. The Epac1-associated proteome is highly enriched with components of the SUMOylation pathway. Activation of Epac1 by intracellular cAMP triggers phase separation and the formation of nuclear condensates containing Epac1 and general components of the SUMOylation machinery to promote cellular SUMOylation. Furthermore, genetic knockout of Epac1 obliterates oxidized low-density lipoprotein–induced cellular SUMOylation in macrophages, leading to suppression of foam cell formation. These results provide a direct nexus connecting two major cellular stress responses to define a molecular mechanism in which cAMP regulates the dynamics of cellular condensates to modulate protein SUMOylation. Stressed out wrestling with SUMO: cAMP-induced Epac1 nuclear condensates accelerate cellular SUMOylation.
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