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Updated: Jun 5, 2025

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Published on: August 7, 2021
Death by ribosome
Anna Constance Vind1, Franklin L Zhong2, Simon Bekker-Jensen1
1Center for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark.
Ribosomes sense cell stress and trigger the ribotoxic stress response (RSR). This pathway, involving ZAKα, p38, and JNK, links ribosome damage to programmed cell death like apoptosis and pyroptosis.
Area of Science:
- Molecular Biology
- Cellular Stress Response
- Programmed Cell Death
Background:
- Ribosomes are crucial for protein synthesis but also act as sensors of cellular stress.
- Stalled or collided ribosomes initiate specific signaling pathways, notably the ribotoxic stress response (RSR).
Purpose of the Study:
- To review recent findings on the connection between ribosome toxicity and programmed cell death.
- To elucidate the role of the RSR pathway in mediating cell death.
- To highlight the physiological relevance of these processes.
Main Methods:
- Review of recent scientific literature.
- Analysis of signaling pathways involved in RSR.
- Examination of cell death mechanisms triggered by ribosome stress.
Main Results:
- The RSR pathway is initiated by ZAKα kinase in response to translational errors.
- RSR activation leads to the downstream activation of stress-activated MAP kinases p38 and JNK.
- The RSR pathway plays a significant role in initiating apoptosis and pyroptosis.
Conclusions:
- Ribosome toxicity is a critical factor in triggering programmed cell death.
- The RSR pathway serves as a key mediator linking ribosome dysfunction to cell death.
- Understanding these links is vital for various physiological conditions.
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