Ribosomal stress-surveillance: three pathways is a magic number.

Ribosomal stress-surveillance: three pathways is a magic number.
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核糖体压力监测:三条途径是一个神奇的数字。

DOI:
10.1093/nar/gkaa757
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发表时间:
2020-11-04
影响因子:
14.9
通讯作者:
Bekker-Jensen S
Bekker-Jensen S
中科院分区:
生物学2区
文献类型:
--
作者:
Vind AC;Genzor AV;Bekker-Jensen S

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细胞依赖于应激反应途径来维持细胞内稳态并限制有害环境刺激的负面影响。应激和促分裂原活化蛋白(MAP)激酶,p38和JNK,是许多应激反应的联系,其中包括核糖毒性应激反应(RSR)。核糖体损伤对细胞功能是有害的,因为它破坏蛋白质合成,增加炎症信号传导,并且如果未解决,则导致细胞死亡。在这篇综述中,我们提供了一个总体概述的三个主要的翻译监督途径:RSR,核糖体相关的质量控制(RQC)和综合应力响应(ISR)。我们强调最近的进展,在定义这些途径的激活机制,并讨论其共性和差异。最后,我们反思RSR的生理作用,并考虑靶向传感激酶ZAKα治疗核糖毒素暴露的治疗潜力。
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.
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