Abstract

Cells rely on stress response pathways to uphold cellular homeostasis and limit the negative effects of harmful environmental stimuli. The stress- and mitogen-activated protein (MAP) kinases, p38 and JNK, are at the nexus of numerous stress responses, among these the ribotoxic stress response (RSR). Ribosomal impairment is detrimental to cell function as it disrupts protein synthesis, increase inflammatory signaling and, if unresolved, lead to cell death. In this review, we offer a general overview of the three main translation surveillance pathways; the RSR, Ribosome-associated Quality Control (RQC) and the Integrated Stress Response (ISR). We highlight recent advances made in defining activation mechanisms for these pathways and discuss their commonalities and differences. Finally, we reflect on the physiological role of the RSR and consider the therapeutic potential of targeting the sensing kinase ZAKα for treatment of ribotoxin exposure.

中文翻译：

---

核糖体应激监测：三个途径是一个神奇的数字。

摘要

细胞依靠应激反应途径维持细胞稳态，并限制有害环境刺激的负面影响。压力和丝裂原活化蛋白（MAP）激酶p38和JNK位于众多应激反应之间，其中包括核糖毒性应激反应（RSR）。核糖体损伤对细胞功能有害，因为它破坏蛋白质合成，增加炎症信号传导，如果不能解决，则会导致细胞死亡。在这篇综述中，我们对三种主要的翻译监视途径进行了概述。RSR，核糖体相关质量控制（RQC）和综合应激反应（ISR）。我们重点介绍了在定义这些途径的激活机制方面取得的最新进展，并讨论了它们的共性和差异。最后，