Phosphorylation of Tudor-SN, a novel substrate of JNK, is involved in the efficient recruitment of Tudor-SN into stress granules
Phosphorylation of Tudor-SN, a novel substrate of JNK, is involved in the efficient recruitment of Tudor-SN into stress granules
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Tudor-SN 是 JNK 的一种新型底物，其磷酸化参与了 Tudor-SN 有效募集到应激颗粒中。
DOI：
10.1016/j.bbamcr.2016.12.018
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发表时间：
2017-03-01
影响因子：
5.1
通讯作者：
Yang, Jie
中科院分区：
文献类型：
--
作者：
Su, Chao;Gao, Xingjie;Yang, Jie
某些应激颗粒（SG）蛋白的翻译后修饰与SG的组装密切相关，SG是一种细胞质灶结构。我们的前期研究表明Tudor葡萄球菌核酸酶（Tudor-SN）蛋白参与了葡萄糖葡萄球菌的形成。然而，尚未报告在强制降解期间潜在Tudor-SN修饰的功能意义。在这项研究中，我们证明了Tudor-SN蛋白在亚砷酸盐刺激后在苏氨酸103（T103）处磷酸化。此外，c-Jun N-末端激酶（JNK）被发现负责T103位点的Tudor-SN磷酸化。我们进一步说明了T103 A突变或JNK抑制剂SP 600125对T103磷酸化的抑制抑制了Tudor-SN向SGs的有效募集。此外，T103 A突变可影响Tudor-SN与G3 BP（Ras-GAP SH 3结构域结合蛋白）蛋白的物理结合，但不影响Tudor-SN与HuR（Hu抗原R）蛋白和AGTR 1 - 3 'UTR（血管紧张素II受体1型的3'-非翻译区）mRNA货物的物理结合。这些数据表明，JNK增强的Tudor-SN磷酸化促进Tudor-SN和G3 BP之间的相互作用，并促进Tudor-SN在亚砷酸钠诱导的氧化应激条件下有效募集到SG中。这一发现为Tudor-SN修饰的生理功能提供了新的见解。(C)2016爱思唯尔B. V.保留所有权利。
Posttranslational modifications of certain stress granule (SG) proteins are closely related to the assembly of SGs, a type of cytoplasmic foci structure. Our previous studies revealed that the Tudor staphylococcal nuclease (Tudor-SN) protein participates in the formation of SGs. However, the functional significance of potential Tudor-SN modifications during stress has not been reported. In this study, we demonstrated that the Tudor-SN protein was phosphorylated at threonine 103 (T103) upon stimulation with arsenite. In addition, c-Jun N-terminal kinase (JNK) was found to be responsible for Tudor-SN phosphorylation at the T103 site. We further illustrated that either a T103A mutation or the suppression of phosphorylation of T103 by the JNK inhibitor SP600125 inhibited the efficient recruitment of Tudor-SN into SGs. In addition, the T103A mutation could affect the physical binding of Tudor-SN with the G3BP (Ras-GAP SH3 domain-binding protein) protein but not with the HuR (Hu antigen R) protein and AGTR1-3'UTR (3'-untranslated region of angiotensin II receptor, type 1) mRNA cargo. These data suggested that JNK-enhanced Tudor-SN phosphorylation promotes the interaction between Tudor-SN and G3BP and facilitates the efficient recruitment of Tudor-SN into SGs under conditions of sodium arsenite-induced oxidative stress. This finding provides novel insights into the physiological function of Tudor-SN modification. (C) 2016 Elsevier B.V. All rights reserved.