Trauma-induced regulation of VHP-1 modulates the cellular response to mechanical stress.
Trauma-induced regulation of VHP-1 modulates the cellular response to mechanical stress.
复制标题
创伤诱导的 VHP-1 调节细胞对机械应力的反应。
DOI：
10.1038/s41467-021-21611-8
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发表时间：
2021-03-05
影响因子：
16.6
通讯作者：
Douglas PM
中科院分区：
文献类型：
--
作者：
Egge N;Arneaud SLB;Fonseca RS;Zuurbier KR;McClendon J;Douglas PM
机械刺激启动适应性信号转导途径，但超过细胞承受物理压力的能力会导致死亡。创伤引起的退化的分子机制仍不清楚。在线虫秀丽隐杆线虫中，我们开发了一种方法来研究细胞变性对钝力创伤引起的机械应力的反应。在此，我们报告身体损伤会激活 c-Jun 激酶 KGB-1，它通过 AP-1 转录复合物调节反应元件。其中，我们发现了一种双特异性 MAPK 磷酸酶 VHP-1，作为神经退行性变的应激诱导调节剂。 VHP-1 调节对机械应力的转录反应，并且其本身会因 KGB-1 介导的去泛素酶 MATH-33 失活和蛋白酶体降解而减弱。我们共同描述了秀丽隐杆线虫中未表征的应激反应途径，并鉴定了转录和翻译后成分，包括 Jun 激酶和磷酸酶活性的反馈环路。神经系统利用适应性策略来减轻创伤引起的神经变性。在这里，作者报告说，MAPK 磷酸酶 VHP-1 是由创伤诱导的，并在秀丽隐杆线虫模型中调节对机械应力的转录反应。
Mechanical stimuli initiate adaptive signal transduction pathways, yet exceeding the cellular capacity to withstand physical stress results in death. The molecular mechanisms underlying trauma-induced degeneration remain unclear. In the nematode C. elegans, we have developed a method to study cellular degeneration in response to mechanical stress caused by blunt force trauma. Herein, we report that physical injury activates the c-Jun kinase, KGB-1, which modulates response elements through the AP-1 transcriptional complex. Among these, we have identified a dual-specificity MAPK phosphatase, VHP-1, as a stress-inducible modulator of neurodegeneration. VHP-1 regulates the transcriptional response to mechanical stress and is itself attenuated by KGB-1-mediated inactivation of a deubiquitinase, MATH-33, and proteasomal degradation. Together, we describe an uncharacterized stress response pathway in C. elegans and identify transcriptional and post-translational components comprising a feedback loop on Jun kinase and phosphatase activity. The nervous system utilizes adaptive strategies to mitigate trauma-induced neurodegeneration. Here, the authors report that a MAPK phosphatase VHP-1 is induced by trauma and regulates transcriptional responses to mechanical stress in a C. elegans model.
DOI：
10.1111/febs.13764
发表时间：
2016-11
期刊：
The FEBS journal
影响因子：
--
作者：
Arneaud SL;Douglas PM
通讯作者：
Douglas PM
抗氨基酶3的抑制作用可保护大鼠脑皮质神经元细胞免受4-羟基-2-非胃胃酸盐和4-羟基-2-非纳纳纳尔的毒性。
影响因子：
3.8
作者：
Tsirulnikov K;Abuladze N;Bragin A;Faull K;Cascio D;Damoiseaux R;Schibler MJ;Pushkin A
通讯作者：
Pushkin A