Sumoylation of eIF4A2 affects stress granule formation.
Sumoylation of eIF4A2 affects stress granule formation.
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DOI：
10.1242/jcs.184614
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发表时间：
2016-06-15
影响因子：
4
通讯作者：
Watts FZ
中科院分区：
文献类型：
--
作者：
Jongjitwimol J;Baldock RA;Morley SJ;Watts FZ
蛋白质合成的调节对于细胞维持活力和防止可能导致肿瘤发生的非计划性增殖至关重要。应激导致翻译停滞，许多翻译起始因子、核糖体亚基和mRNA被隔离到应激颗粒或P体中。这允许翻译机器的重新编程。翻译的许多方面都受到翻译后修饰的调控。几个蛋白质组学筛选已确定翻译起始因子作为类小泛素化的靶点，尽管在许多情况下这种修饰的作用尚未确定。我们发现eIF 4A 2被SUMO修饰，在单个残基（K226）上发生SUMO化。我们证明，sumoylation的eIF 4A 2是适度增加响应亚砷酸盐和电离辐射，但减少响应热休克或马尿酸。在亚砷酸盐处理的细胞中，而不是在马尿酸处理的细胞中，eIF 4A 2被募集到应激颗粒，这表明eIF 4A 2的sumoylation与其募集到应激颗粒相关。此外，我们证明了不能sumoylate eIF 4A 2的结果受损的应激颗粒形成，表明sumoylation在应激反应中的新作用。总结：在应激反应中，启动蛋白质合成所需的蛋白质被修饰;我们证明了eIF 4A 2的sumoylation与其向应激颗粒的募集相关。
Regulation of protein synthesis is crucial for cells to maintain viability and to prevent unscheduled proliferation that could lead to tumorigenesis. Exposure to stress results in stalling of translation, with many translation initiation factors, ribosomal subunits and mRNAs being sequestered into stress granules or P bodies. This allows the re-programming of the translation machinery. Many aspects of translation are regulated by post-translational modification. Several proteomic screens have identified translation initiation factors as targets for sumoylation, although in many cases the role of this modification has not been determined. We show here that eIF4A2 is modified by SUMO, with sumoylation occurring on a single residue (K226). We demonstrate that sumoylation of eIF4A2 is modestly increased in response to arsenite and ionising radiation, but decreases in response to heat shock or hippuristanol. In arsenite-treated cells, but not in hippuristanol-treated cells, eIF4A2 is recruited to stress granules, suggesting sumoylation of eIF4A2 correlates with its recruitment to stress granules. Furthermore, we demonstrate that the inability to sumoylate eIF4A2 results in impaired stress granule formation, indicating a new role for sumoylation in the stress response. Summary: In response to stress, proteins required to initiate protein synthesis are modified; we demonstrate that sumoylation of eIF4A2 correlates with its recruitment to stress granules.