Snail modulates JNK-mediated cell death in Drosophila
Snail modulates JNK-mediated cell death in Drosophila
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蜗牛调节果蝇 JNK 介导的细胞死亡
DOI：
10.1038/s41419-019-2135-7
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发表时间：
2019
影响因子：
9
通讯作者：
Lei Xue
中科院分区：
文献类型：
--
作者：
Chenxi Wu;Zhuojie Li;Xiang Ding;Lei Xue
细胞死亡在动物发育和组织稳态中起着关键作用。这一过程的失调与多种人类疾病有关，包括发育和免疫疾病、神经退行性疾病和肿瘤。虽然JNK通路在细胞死亡中的基本作用已被广泛研究，但其下游调控因子及其潜在机制仍在很大程度上难以捉摸。从果蝇基因筛选中，我们发现蜗牛（Sna），一种锌指转录因子，作为异位egr诱导的jnk介导的细胞死亡的新调节剂。此外，sna对于JNK信号在发育过程中的生理功能至关重要。我们的遗传上位数据表明，Sna在JNK的下游作用，促进细胞死亡。在机制上，JNK信号触发dfoxo依赖的sna转录激活。因此，我们的研究结果不仅揭示了Sna在调节JNK介导的细胞死亡中的新功能和潜在机制，而且为JNK信号相关疾病提供了潜在的药物靶点和治疗策略。
Cell death plays a pivotal role in animal development and tissue homeostasis. Dysregulation of this process is associated with a wide variety of human diseases, including developmental and immunological disorders, neurodegenerative diseases and tumors. While the fundamental role of JNK pathway in cell death has been extensively studied, its down-stream regulators and the underlying mechanisms remain largely elusive. From a Drosophila genetic screen, we identified Snail (Sna), a Zinc-finger transcription factor, as a novel modulator of ectopic Egr-induced JNK-mediated cell death. In addition, sna is essential for the physiological function of JNK signaling in development. Our genetic epistasis data suggest that Sna acts downstream of JNK to promote cell death. Mechanistically, JNK signaling triggers dFoxO-dependent transcriptional activation of sna. Thus, our findings not only reveal a novel function and the underlying mechanism of Sna in modulating JNK-mediated cell death, but also provide a potential drug target and therapeutic strategies for JNK signaling-related diseases.