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Ribotoxic Stress Response: Coordinating Pyroptosis and Apoptosis
Jie Sun1,2, Yiyun Zhang3, Lisha Yan3
1Department of Pathogenic Biology, College of Basic Medical Sciences, Jilin Medical University, Jilin City, People's Republic of China.
Abstract:
Ribotoxic stress response (RSR) is a translation-linked stress pathway that emerges when ribosomes stall and collide. Its upstream trigger is the MAP3K/ZAKα, a leucine-zipper- and SAM-containing kinase that relays ribotoxic stress to downstream programs shaping metabolism, immune signaling, and cell-fate decisions. Increasing evidence suggests that RSR also connects two major forms of programmed cell death-apoptosis and pyroptosis-by coordinating signaling crosstalk that shapes death outcomes. Disruption of this regulatory axis is associated with chronic inflammatory disorders, immune dysfunction, and malignancy. Here, we summarize current knowledge on the molecular mechanisms through which RSR interfaces with apoptotic and pyroptotic pathways, and we discuss its roles in cellular homeostasis and disease. Clarifying how RSR regulates cell-death signaling could guide the development of targeted therapeutic strategies for conditions involving dysregulated inflammation and cell death.
Insights
The ribotoxic stress response (RSR) links ribosome stalling to cell death pathways like apoptosis and pyroptosis. Understanding RSR
Area of Science:
- Molecular Biology
- Cellular Biology
- Immunology
Background:
- Ribotoxic stress response (RSR) is a translation-dependent stress pathway triggered by ribosome stalling.
- MAP3K/ZAKα kinase initiates RSR, influencing metabolism, immune signaling, and cell fate.
- RSR is increasingly recognized for its role in coordinating apoptosis and pyroptosis.
Purpose of the Study:
- To summarize current knowledge on RSR's molecular mechanisms.
- To elucidate RSR's interface with apoptotic and pyroptotic pathways.
- To discuss RSR's roles in cellular homeostasis and disease.
Main Methods:
- Literature review and synthesis of existing research.
- Analysis of molecular signaling pathways.
- Discussion of RSR's implications in disease.
Main Results:
- RSR acts as a crucial link between ribosome stress and programmed cell death.
- RSR coordinates signaling crosstalk between apoptosis and pyroptosis.
- Dysregulation of RSR is implicated in inflammatory disorders, immune dysfunction, and cancer.
Conclusions:
- RSR plays a significant role in regulating cell death outcomes.
- Targeting RSR could offer therapeutic strategies for diseases involving inflammation and cell death.
- Further clarification of RSR's mechanisms is needed for therapeutic development.
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