Ribosomal stress-surveillance: three pathways is a magic number

Anna Constance Vind, Aitana Victoria Genzor, Simon Bekker-Jensen

Research output: Contribution to journalJournal articleResearchpeer-review

79 Citations (Scopus)
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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.

Original languageEnglish
JournalNucleic Acids Research
Volume48
Issue number19
Pages (from-to)10648-10661
Number of pages14
ISSN0305-1048
DOIs
Publication statusPublished - 2020

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