ArticleCell death & disease2024
Sensing of endogenous retroviruses-derived RNA by ZBP1 triggers PANoptosis in DNA damage and contributes to toxic side effects of chemotherapy.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Tumour-associated dsRNA accumulation and innate immune activation: mechanistic basis and therapeutic strategies.EBioMedicine · 2026Review
- Remodeling the Immune Landscape: How Obesity-Induced SASPs Create a Pro-Tumorigenic Niche.Current obesity reports · 2026Review
- Targeting the non-coding RNA-PANoptosis axis: a novel frontier in disease diagnosis and therapy.Apoptosis : an international journal on programmed cell death · 2026Review
- Immune response to DNA and RNA: structural insights, molecular mechanisms, and therapeutic targeting.Molecular biomedicine · 2026Review
- Piroctone olamine promotes BECN1 transcription and activates autophagy by targeting HDAC6 in colorectal cancer.Acta pharmacologica Sinica · 2026Article
- PANoptosis in life and death across cell types: From innate immunity to therapeutic implications.Cell chemical biology · 2026Review
- Review
- Pseudorabies virus infection induces IRF1-dependent PANoptosis to provoke the excessive release of HMGB1 and IL-1β.Communications biology · 2026Article
- Mitochondrial dysfunction drives ZBP1-mediated PANoptosis to increase the susceptibility of heart failure with preserved ejection fraction-associated atrial fibrillation.Journal of advanced research · 2026Article
- [Role of programmed cell death in platinum resistance in ovarian cancer].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- Role of PANoptosis in intestinal diseases and its therapeutic implications.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Defining critical roles for ZBP1 in PANoptosis utilizing a novel genetic tool for disease modeling and therapeutic development.bioRxiv : the preprint server for biology · 2026Article
- ZBP1's Inability to Convert Unmodified RNAs to the Z-form Underlies a Balanced Mechanism of RNA Recognition with ADAR1.bioRxiv : the preprint server for biology · 2026Article
- STING-STAT1-ZBP1 axis orchestrates PANoptotic signaling in ischemia-reperfusion induced acute kidney injury.Cell communication and signaling : CCS · 2026Article
- Cell-Free DNA-Based Theranostics for Inflammatory Disorders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Activation of endogenous retroviruses in tumor cells and their immunomodulatory mechanisms: from molecular basis to clinical translation.Frontiers in oncology · 2026Review
- Mitochondrial dysfunction-driven PANoptosis in doxorubicin-induced cardiotoxicity: mechanistic insights and intervention strategies.Frontiers in pharmacology · 2026Review
- Epigenetic regulation of PANoptosis: DNA methylation, histone modifications and non-coding RNAs.EXCLI journal · 2026Review
- Emerging role of PANoptosis in pathogen infection and systemic diseases.Cell biology and toxicology · 2025Review
- PANoptosis: potential new targets and therapeutic prospects in digestive diseases.Apoptosis : an international journal on programmed cell death · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
17 authors.
Funding
Abstract
Excessive DNA damage triggers various types of programmed cell death (PCD), yet the regulatory mechanism of DNA damage-induced cell death is not fully understood. Here, we report that PANoptosis, a coordinated PCD pathway, including pyroptosis, apoptosis and necroptosis, is activated by DNA damage. The Z-DNA binding protein 1 (ZBP1) is the apical sensor of PANoptosis and essential for PANoptosome assembly in response to DNA damage. We find endogenous retroviruses (ERVs) are activated by DNA damage and act as ligands for ZBP1 to trigger PANoptosis. By using ZBP1 knock-out and knock-in mice disrupting ZBP1 nucleic acid-binding activity, we demonstrate that ZBP1-mediated PANoptosis contributes to the toxic effects of chemotherapeutic drugs, which is dependent on ZBP1 nucleic acid-binding activity. We found that ZBP1 expression is downregulated in tumor tissue. Furthermore, in colorectal cancer patients, dsRNA is induced by chemotherapy and sensed by ZBP1 in normal colonic tissues, suggesting ZBP1-mediated PANoptosis is activated by chemotherapy in normal tissues. Our findings indicate that ZBP1-mediated PANoptosis is activated by DNA damage and contributes to the toxic side effects of DNA-damage-based chemotherapy. These data suggest that ZBP1 could be a promising therapeutic target to alleviate chemotherapy-related side effects.
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