Stress-induced release of Oct-1 from the nuclear envelope is mediated by JNK phosphorylation of lamin B1.
Stress-induced release of Oct-1 from the nuclear envelope is mediated by JNK phosphorylation of lamin B1.
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DOI：
10.1371/journal.pone.0177990
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Vaux DJ
中科院分区：
文献类型：
--
作者：
Boubriak II;Malhas AN;Drozdz MM;Pytowski L;Vaux DJ
核层可以结合和隔离转录因子(TF)，如果核层异常，这一功能就会与缺失或突变的层粘连蛋白结合。我们现在表明，转移因子的隔离不是全有或全无，而是对外部信号的动态生理反应。我们发现，在化学甲基化试剂甲基甲烷磺酸(MMS)引起的细胞应激条件下，无处不在的转铁蛋白Oct-1与Lamin B1的结合被逆转。使用激酶抑制剂对可能介导Oct-1结合变化的lamin B1翻译后修饰的研究发现了c-Jun氨基末端激酶(JNK)的作用。从对照和MMS处理的细胞核中分离的lamin B1的磷酸蛋白质组学和定点突变分析表明，T575是应激后磷酸化的JNK位点。一种新的磷酸化T575特异性抗肽抗体证实，细胞暴露在特定应激条件下后，细胞T575间期磷酸化增加，使我们能够得出结论，Lamin B1作为间期激酶靶标，释放Oct-1来执行对应激的保护性反应。
The nuclear lamina can bind and sequester transcription factors (TFs), a function lost if the lamina is abnormal, with missing or mutant lamin proteins. We now show that TF sequestration is not all-or-nothing, but a dynamic physiological response to external signals. We show that the binding of the ubiquitous TF, Oct-1, to lamin B1 was reversed under conditions of cellular stress caused, inter alia, by the chemical methylating agent methylmethanesulfonate (MMS). A search for lamin B1 post-translational modifications that might mediate changes in Oct-1 binding using kinase inhibitors uncovered a role for c-Jun N-terminal kinase (JNK). Phosphoproteomic and site-directed mutagenesis analyses of lamin B1 isolated from control and MMS-treated nuclei identified T575 as a JNK site phosphorylated after stress. A new phospho-T575 specific anti-peptide antibody confirmed increased interphase cellular T575 phosphorylation after cell exposure to certain stress conditions, enabling us to conclude that lamin B1 acts as an interphase kinase target, releasing Oct-1 to execute a protective response to stress.