ArticleCell death and differentiation2024
ZBP1 causes inflammation by inducing RIPK3-mediated necroptosis and RIPK1 kinase activity-independent apoptosis.
Article in Cell death and differentiation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed.
- Biological consequences of Z-nucleic acid sensing by ZBP1 and ADAR1.RNA biology · 2026Review
- Role of PANoptosis in cancer: molecular mechanisms and therapeutic insights.Archives of toxicology · 2026Review
- ZBP1 at the Interface of Nucleic-Acid Stress and Inflammatory Cell Death After Intracerebral Hemorrhage: A Hypothesis-Driven Overview.Neurochemical research · 2026Review
- Programmed cell death in inflammation: interactions and holistic perspective.Cellular & molecular immunology · 2026Review
- Intratumoral T cell activation kills tumors regardless of T cell specificity.Nature immunology · 2026Article
- Mechanisms, regulation and clinical relevance of necroptosis.Nature reviews. Molecular cell biology · 2026Review
- GEF-H1 upon microtubule destabilization drives ZBP1-dependent necroptosis.Cell death and differentiation · 2026Article
- Cellular senescence and regulated cell death in cancer: mechanisms, cross-regulatory networks and therapeutic implications.Journal of hematology & oncology · 2026Review
- Truncating RELA variants drive autoinflammation and autoimmunity by impairing the negative feedback control of NF-κB.JCI insight · 2026Article
- The Role of cGAS-STING-Driven PANoptosis in Neurodegenerative Diseases and Therapeutic Prospects.Cells · 2026Review
- Mitochondrial homeostasis imbalance-triggered PANoptosis in traumatic brain and spinal cord injury: from mechanism to therapeutic strategies.Redox biology · 2026Review
- ZBP1 in Neuroinflammation and Neurodegeneration: Z-Nucleic-Acid Sensing, RHIM Signalling and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- Transcriptomic profiling of HBV transgenic mouse livers reveals ZBP1-associated necroptotic signaling.Scientific reports · 2026Article
- Review
- PANoptosis in life and death across cell types: From innate immunity to therapeutic implications.Cell chemical biology · 2026Review
- Oncogenic KRAS-driven type I interferon signalling primes pancreatic cancer for necroptosis.Nature communications · 2026Article
- What does BCL-2 do? From new molecular insights to the clinical implications.Cell death and differentiation · 2026Review
- PANoptosis as a drug discovery framework: integrating cell death architecture with clinical translation.Genes and immunity · 2026Review
- ZBP1 promotes RIPK1-dependent apoptosis in aristolochic acid nephropathy.Zoological research · 2026Article
- Loss of MLKL impairs abdominal aortic aneurysm development by attenuating smooth muscle cell necroptosis.Cell death & disease · 2026Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Z-DNA binding protein 1 (ZBP1) has important functions in anti-viral immunity and in the regulation of inflammatory responses. ZBP1 induces necroptosis by directly engaging and activating RIPK3, however, the mechanisms by which ZBP1 induces inflammation and in particular the role of RIPK1 and the contribution of cell death-independent signaling remain elusive. Here we show that ZBP1 causes skin inflammation by inducing RIPK3-mediated necroptosis and RIPK1-caspase-8-mediated apoptosis in keratinocytes. ZBP1 induced TNFR1-independent skin inflammation in mice with epidermis-specific ablation of FADD by triggering keratinocyte necroptosis. Moreover, transgenic expression of C-terminally truncated constitutively active ZBP1 (ZBP1ca) in mouse epidermis caused skin inflammation that was only partially inhibited by abrogation of RIPK3-MLKL-dependent necroptosis and fully prevented by combined deficiency in MLKL and caspase-8. Importantly, ZBP1ca induced caspase-8-mediated skin inflammation by RHIM-dependent but kinase activity-independent RIPK1 signaling. Furthermore, ZBP1ca-induced inflammatory cytokine production in the skin was completely prevented by combined inhibition of apoptosis and necroptosis arguing against a cell death-independent pro-inflammatory function of ZBP1. Collectively, these results showed that ZBP1 induces inflammation by activating necroptosis and RIPK1 kinase activity-independent apoptosis.
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Registered trials
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