ArticlePLoS biology2025
RIPK1 is required for ZBP1-driven necroptosis in human cells.
Article in PLoS biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Biological consequences of Z-nucleic acid sensing by ZBP1 and ADAR1.RNA biology · 2026Review
- Mechanisms, regulation and clinical relevance of necroptosis.Nature reviews. Molecular cell biology · 2026Review
- Z-Nucleic Acid-Binding Protein (ZBP)1 (DAI/DLM1) Regulation in Antiviral Cell Death Pathways.Pathogens (Basel, Switzerland) · 2026Review
- Human ZBP1 is a potent inducer of cell death through mechanisms divergent from mouse ZBP1.EMBO reports · 2026Article
- Cell death network regulation in HSV infection: immune evasion versus host defense.Apoptosis : an international journal on programmed cell death · 2026Review
- Species-specific regulation of necroptosis by STK38-dependent RIPK1 phosphorylation.Cell death and differentiation · 2026Article
- Regulated cell death programs shaping cancer therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Solution NMR reveals micelle-stabilized α-helical segments flanking the RIPK1 RHIM amyloid core.Biochemical and biophysical research communications · 2026Article
- The landscape of regulated cell death: It's all downhill from here.Molecular cell · 2026Review
- Regulatory complexity and therapeutic targeting of the necroptosis network.Frontiers in immunology · 2026Review
- Apoptosis as an evolutionary battleground: pathogen pressure and the shaping of programmed cell death pathways.Frontiers in cell and developmental biology · 2026Review
- Necroptosis in asthma: a critical driver of immune dysregulation and airway remodeling.Frontiers in immunology · 2026Review
- Foot-and-mouth disease virus non-structural protein 3D induces necroptosis through interaction with RIPK3 in PK-15 and BHK-21 cells.Frontiers in veterinary science · 2026Article
- ZBP1 as a dynamic monitor of viral replication: implications for therapeutic strategies.Frontiers in cellular and infection microbiology · 2026Review
- Necroptotic cell death consequences and disease relevance.Nature immunology · 2025Review
- Zbp1 promotes atherosclerosis and lesion necrosis in mice.Atherosclerosis · 2025Article
- Structural basis for amyloid fibril assembly by the master cell-signaling regulator receptor-interacting protein kinase 1.Nature communications · 2025Article
- Targeting the redox-programmed cell death axis in breast cancer: from molecular mechanisms to therapeutic resistance.Cell death discovery · 2025Review
- Mixed Lineage Kinase Domain-Like Protein (MLKL): From Mechanisms to Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- PANoptosis: Cross-Talk Among Apoptosis, Necroptosis, and Pyroptosis in Neurological Disorders.Journal of inflammation research · 2025Review
Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
Necroptosis initiated by the host sensor Z-NA binding protein 1 (ZBP1) is essential for host defense against a growing number of viruses, including herpes simplex virus 1 (HSV-1). Studies with HSV-1 and other necroptogenic stimuli in murine settings have suggested that ZBP1 triggers necroptosis by directly complexing with the kinase RIPK3. Whether this is also the case in human cells, or whether additional co-factors are needed for ZBP1-mediated necroptosis, is unclear. Here, we show that ZBP1-induced necroptosis in human cells requires RIPK1. We have found that RIPK1 is essential for forming a stable and functional ZBP1-RIPK3 complex in human cells, but is dispensable for the formation of the equivalent murine complex. The receptor-interacting protein (RIP) homology interaction motif (RHIM) in RIPK3 is responsible for this difference between the 2 species, because replacing the RHIM in human RIPK3 with the RHIM from murine RIPK3 is sufficient to overcome the requirement for RIPK1 in human cells. These observations describe a critical mechanistic difference between mice and humans in how ZBP1 engages in necroptosis, with important implications for treating human diseases.
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Registered trials
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