ArticleEMBO reports2022
Human ZBP1 induces cell death-independent inflammatory signaling via RIPK3 and RIPK1.
Article in EMBO reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 77 citations in OpenAlex.
- Biological consequences of Z-nucleic acid sensing by ZBP1 and ADAR1.RNA biology · 2026Review
- Human ZBP1 is a potent inducer of cell death through mechanisms divergent from mouse ZBP1.EMBO reports · 2026Article
- ZBP1 mediated restriction of Toxoplasma gondii in both the early acute and chronic brain stages of infection.ImmunoHorizons · 2026Article
- Neuron-derived mitochondrial DNA (mtDNA) activates microglia via the Z-DNA binding protein 1 (ZBP1)-mediated pathway in mild traumatic brain injury.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- The landscape of regulated cell death: It's all downhill from here.Molecular cell · 2026Review
- Metabolic and post-translational modifications in sepsis-associated immune dysfunction: a conceptual framework.Frontiers in immunology · 2026Review
- PANoptosis nexus in ischemia-reperfusion injury: from integrated cell death mechanisms to novel therapeutic opportunities.Frontiers in immunology · 2026Review
- Delaying cardiac aging: potential mechanisms centered on PANoptosis and targeted intervention strategies.Frontiers in cardiovascular medicine · 2026Review
- PANoptosis: a new perspective for targeting programmed cell death after spinal cord injury.Frontiers in immunology · 2026Review
- ZBP1 as a dynamic monitor of viral replication: implications for therapeutic strategies.Frontiers in cellular and infection microbiology · 2026Review
- Cromolyn as a novel pharmacophore of the Zα domain of the RNA-editing enzyme ADAR1p150.Protein science : a publication of the Protein Society · 2025Article
- Necroptotic cell death consequences and disease relevance.Nature immunology · 2025Review
- An atlas of ferroptosis-induced secretomes.Cell death and differentiation · 2025Article
- SPOP mediates apoptosis and protects against necroptosis by regulating ubiquitination of RIPK1 and RIPK3.JCI insight · 2025Article
- Geniposide protects against cerebral ischemic injury by targeting SOX2/RIPK1 axis.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- PANoptosis in cancer: molecular mechanisms and therapeutic potential.Cancer gene therapy · 2025Review
- Astrocytic RIPK3 exerts protective anti-inflammatory activity in mice with viral encephalitis by transcriptional induction of serpins.Science signaling · 2025Article
- MLKL‒OPTN axis regulates herpesvirus-induced neurological sequelae.Clinical and translational medicine · 2025Article
- RIPK3 coordinates RHIM domain-dependent antiviral inflammatory transcription in neurons.Science signaling · 2025Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 5 countries.
Funding
Abstract
ZBP1 is an interferon-induced cytosolic nucleic acid sensor that facilitates antiviral responses via RIPK3. Although ZBP1-mediated programmed cell death is widely described, whether and how it promotes inflammatory signaling is unclear. Here, we report a ZBP1-induced inflammatory signaling pathway mediated by K63- and M1-linked ubiquitin chains, which depends on RIPK1 and RIPK3 as scaffolds independently of cell death. In human HT29 cells, ZBP1 associated with RIPK1 and RIPK3 as well as ubiquitin ligases cIAP1 and LUBAC. ZBP1-induced K63- and M1-linked ubiquitination of RIPK1 and ZBP1 to promote TAK1- and IKK-mediated inflammatory signaling and cytokine production. Inhibition of caspase activity suppressed ZBP1-induced cell death but enhanced cytokine production in a RIPK1- and RIPK3 kinase activity-dependent manner. Lastly, we provide evidence that ZBP1 signaling contributes to SARS-CoV-2-induced cytokine production. Taken together, we describe a ZBP1-RIPK3-RIPK1-mediated inflammatory signaling pathway relayed by the scaffolding role of RIPKs and regulated by caspases, which may induce inflammation when ZBP1 is activated below the threshold needed to trigger a cell death response.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.