Deubiquitylases USP5 and USP13 are recruited to and regulate heat-induced stress granules through their deubiquitylating activities
Deubiquitylases USP5 and USP13 are recruited to and regulate heat-induced stress granules through their deubiquitylating activities
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DOI：
10.1242/jcs.210856
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发表时间：
2018-04
影响因子：
4
通讯作者：
Xuan Xie;S. Matsumoto;Akinori Endo;T. Fukushima;H. Kawahara;Y. Saeki;M. Komada
中科院分区：
文献类型：
--
作者：
Xuan Xie;S. Matsumoto;Akinori Endo;T. Fukushima;H. Kawahara;Y. Saeki;M. Komada
摘要应激颗粒是由各种应激诱导的短暂胞质聚集体，其中含有停滞的mRNA和RNA结合蛋白。它们被认为调节mRNA翻译和应激反应。在这里，我们表明，去泛素化酶USP 5和USP 13被招募到热诱导的应激颗粒。热应激颗粒还含有K48和K63连接的泛素链。USP 5或USP 13的耗尽导致泛素链水平升高和热诱导应激颗粒的加速组装，表明这些酶通过其泛素异肽酶活性调节应激颗粒的稳定性。此外，分解的热诱导的应力颗粒后，返回到正常温度的细胞显着抑制个别耗尽的USP 5或USP 13。最后，过表达的泛素突变体缺乏的C-末端双甘氨酸基序引起的积累未锚定的泛素链和热诱导的应力颗粒的解体的镇压。由于未锚定的泛素链是USP 5的优选底物，我们认为USP 5通过介导未锚定的泛素链的水解来调节热诱导的应激颗粒的组装和拆卸，而USP 13通过去泛素化蛋白缀合的泛素链来调节应激颗粒。这篇文章有一个相关的第一人称采访的论文的第一作者。总结：两种相似的去泛素化酶USP 5和USP 13位于热应激诱导的应激颗粒中，并促进它们的分解，最有可能是通过水解泛素链。
ABSTRACT Stress granules are transient cytoplasmic foci induced by various stresses that contain translation-stalled mRNAs and RNA-binding proteins. They are proposed to modulate mRNA translation and stress responses. Here, we show that the deubiquitylases USP5 and USP13 are recruited to heat-induced stress granules. Heat-induced stress granules also contained K48- and K63-linked ubiquitin chains. Depletion of USP5 or USP13 resulted in elevated ubiquitin chain levels and accelerated assembly of heat-induced stress granules, suggesting that these enzymes regulate the stability of the stress granules through their ubiquitin isopeptidase activity. Moreover, disassembly of heat-induced stress granules after returning the cells to normal temperatures was markedly repressed by individual depletion of USP5 or USP13. Finally, overexpression of a ubiquitin mutant lacking the C-terminal diglycine motif caused the accumulation of unanchored ubiquitin chains and the repression of the disassembly of heat-induced stress granules. As unanchored ubiquitin chains are preferred substrates for USP5, we suggest that USP5 regulates the assembly and disassembly of heat-induced stress granules by mediating the hydrolysis of unanchored ubiquitin chains while USP13 regulates stress granules through deubiquitylating protein-conjugated ubiquitin chains. This article has an associated First Person interview with the first author of the paper. Summary: Two similar deubiquitylases USP5 and USP13 are located in stress granules induced by heat stress and facilitate their disassembly, most likely through hydrolysis of ubiquitin chains.