Affinage

ZBP1

Z-DNA-binding protein 1 · UniProt Q9H171

Round 2 corrected
Length
429 aa
Mass
46.3 kDa
Annotated
2026-04-28
130 papers in source corpus 45 papers cited in narrative 42 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ZBP1 is an interferon-inducible innate immune sensor that detects left-handed Z-form nucleic acids—including viral Z-RNA, endogenous retroelement-derived Z-RNA, telomeric RNA (TERRA), and mitochondrial Z-DNA—through its tandem Zα domains, thereby initiating inflammatory cell death and type I interferon production (PMID:32296175, PMID:36755096, PMID:37352855, PMID:41082924). Upon ligand binding, ZBP1 oligomerizes and recruits RIPK3 (and RIPK1) via RHIM-dependent amyloid-like cross-polymerization to activate parallel cell death pathways—MLKL-dependent necroptosis, caspase-8-mediated apoptosis, and NLRP3/caspase-1-driven pyroptosis (collectively termed PANoptosis)—while also engaging MAVS on mitochondria and cooperating with cGAS-STING to amplify interferon signaling (PMID:22423968, PMID:27917412, PMID:38982083, PMID:36755096). RIPK1's RHIM domain competitively restrains ZBP1–RIPK3 engagement, and ADAR1 edits endogenous Z-RNA to prevent sterile ZBP1 activation; loss of either checkpoint causes ZBP1-dependent autoinflammatory pathology rescued by ZBP1 ablation (PMID:27819681, PMID:35859177, PMID:35859176). A short splice isoform (ZBP1-S) retaining Zα domains but lacking RHIMs acts as an endogenous competitive inhibitor of full-length ZBP1-driven cell death and inflammation (PMID:39300211).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2001 High

    Determining how ZBP1 recognizes left-handed Z-DNA established the structural basis for its nucleic acid sensing: the Zα domain adopts a winged-helix fold with a Z-DNA-specific contact surface shared with ADAR1, defining a Z-nucleic acid binding protein family.

    Evidence X-ray crystallography of DLM-1 Zα domain bound to Z-DNA at 1.85 Å resolution

    PMID:11524677

    Open questions at the time
    • Structure of full-length ZBP1 with ligand not determined
    • Z-RNA binding mode not yet addressed
    • No signaling pathway identified
  2. 2007 High

    Identifying ZBP1 as a cytosolic DNA sensor that activates type I interferon through IRF3/TBK1 recruitment revealed its first signaling function, and forced dimerization showed that oligomerization is sufficient for pathway activation independently of DNA.

    Evidence RNAi knockdown, co-immunoprecipitation of DAI with IRF3 and TBK1, forced dimerization constructs, reporter assays in mouse fibroblasts

    PMID:17618271 PMID:18375758

    Open questions at the time
    • Whether DNA is the physiologically relevant ligand in vivo was unresolved
    • Downstream effector mechanisms (cell death vs. transcription) not yet distinguished
  3. 2009 High

    Discovery that ZBP1 contains two RHIM domains that recruit RIPK1 and RIPK3 for NF-κB activation connected ZBP1 to the necroptosis signaling machinery and explained how MCMV M45 protein blocks ZBP1 signaling.

    Evidence Co-immunoprecipitation, RNAi, NF-κB reporter assays, RHIM domain mapping

    PMID:19590578

    Open questions at the time
    • Whether ZBP1-RIPK3 interaction directly triggers cell death not yet demonstrated
    • RHIM-RHIM interaction structure unresolved
  4. 2012 High

    Establishing that ZBP1 forms a RHIM-dependent complex with RIPK3 to drive virus-induced programmed necrosis during MCMV infection positioned ZBP1 as the upstream sensor in virus-triggered necroptosis, analogous to RIPK1 in death receptor signaling.

    Evidence ZBP1 knockout mice and cells, co-immunoprecipitation, MCMV infection with vIRA mutant analysis, in vivo mouse models

    PMID:22423968

    Open questions at the time
    • Identity of the viral molecular pattern sensed by ZBP1 remained unknown
    • Whether ZBP1 senses RNA versus DNA during infection not resolved
  5. 2016 High

    Two simultaneous studies showed that RIPK1's RHIM domain acts as a physiological brake on ZBP1–RIPK3 necroptosis: RIPK1 RHIM mutation caused perinatal lethality fully rescued by ZBP1 deletion, revealing the competitive RHIM engagement model that governs ZBP1 signaling homeostasis.

    Evidence RIPK1 RHIM mutant knock-in mice, epistatic crosses with ZBP1/RIPK3/MLKL knockouts, co-immunoprecipitation

    PMID:27819681 PMID:27819682

    Open questions at the time
    • Mechanism by which RIPK1 DD contributes to ZBP1 restraint not yet explored
    • Whether endogenous ligands activate ZBP1 in RIPK1-mutant context unknown
  6. 2016 High

    Demonstrating that ZBP1 senses influenza A virus to trigger simultaneous apoptosis, necroptosis, and pyroptosis (PANoptosis) through RIPK3, caspase-8, and NLRP3 expanded ZBP1's role from a necroptosis sensor to an apical orchestrator of multiple cell death modalities.

    Evidence ZBP1 knockout mice, co-immunoprecipitation, cell death assays, in vivo IAV infection models

    PMID:27917412

    Open questions at the time
    • Nature of the viral ligand (protein vs. nucleic acid) not definitively resolved
    • How ZBP1 interfaces with the NLRP3 inflammasome mechanistically unclear
  7. 2017 High

    Showing that MCMV-induced ZBP1 activation requires viral early gene transcription and the Zα2 domain—but not input virion DNA—shifted the paradigm from DNA sensing to RNA sensing, implicating viral RNA transcripts as the biologically relevant ZBP1 ligand.

    Evidence Viral transcription mutant analysis, Zα2 domain deletions, cell death assays

    PMID:28607035

    Open questions at the time
    • Direct binding of ZBP1 to Z-form RNA not yet demonstrated
    • Whether Z-RNA forms during infection not visualized
  8. 2020 High

    Visualization of Z-RNA in the nucleus of IAV-infected cells and demonstration that nuclear ZBP1 activates RIPK3-MLKL inside the nucleus to disrupt the nuclear envelope established the 'inside-out' death pathway and confirmed Z-RNA as the physiological viral ligand.

    Evidence Z-RNA immunofluorescence, nuclear fractionation, RIPK3/MLKL knockouts, confocal live-cell imaging, in vivo models

    PMID:32200799

    Open questions at the time
    • Source of Z-RNA (viral vs. host) not distinguished
    • Nuclear MLKL activation mechanism not structurally characterized
  9. 2020 High

    Demonstrating that ZBP1 Zα domains sense endogenous Z-form nucleic acids from retroelement-derived dsRNA to trigger RIPK3-dependent necroptosis in uninfected cells established ZBP1 as a sensor of sterile self-nucleic acids, not only pathogen-associated patterns.

    Evidence Zα domain knock-in mice with disrupted nucleic acid binding, RNA immunoprecipitation, endogenous retroelement RNA sequencing, multiple conditional KO mice

    PMID:32296175

    Open questions at the time
    • Specific endogenous RNA species serving as ligands not fully mapped
    • Physiological contexts for sterile ZBP1 activation beyond genetic models unclear
  10. 2022 High

    Three simultaneous studies demonstrated that ADAR1 is the master negative regulator of ZBP1: ADAR1 edits endogenous Alu-element-derived Z-RNAs to prevent their recognition by ZBP1, and all ADAR1 mutation-driven autoinflammatory pathology is fully rescued by ZBP1 ablation, establishing the ADAR1–ZBP1 axis as a central checkpoint in innate immune homeostasis.

    Evidence ADAR1 Zα mutant knock-in mice, ZBP1 KO epistasis, RIPK3/MLKL/caspase-8 KO combinations, endogenous Alu-element RNA sequencing, Z-RNA immunofluorescence, in vivo tumor models

    PMID:35614224 PMID:35859175 PMID:35859176 PMID:35859177

    Open questions at the time
    • Complete catalog of endogenous Z-RNA ligands not established
    • Whether ADAR1 editing efficiency varies across tissues to modulate ZBP1 activation unknown
    • ZBP1 promotes IFN independently of RIPK3/MLKL/caspase-8 in one genetic model—mechanism undefined
  11. 2023 High

    Two studies revealed non-canonical ZBP1 signaling platforms: ZBP1 cooperates with cGAS on mitochondrial Z-DNA to sustain STAT1/IFN signaling via a cytosolic ZBP1–cGAS–RIPK1–RIPK3 complex, and ZBP1 oligomerizes into filaments on the outer mitochondrial membrane upon binding telomeric RNA (TERRA) to activate MAVS-dependent interferon responses during replicative crisis.

    Evidence Co-immunoprecipitation of ZBP1-cGAS-RIPK1-RIPK3 complex, ZBP1 KO mice in doxorubicin cardiotoxicity model; RNA immunoprecipitation of ZBP1-TERRA, super-resolution/electron microscopy of mitochondrial ZBP1 filaments, ZBP1-MAVS co-IP

    PMID:36755096 PMID:37352855

    Open questions at the time
    • Structural basis for ZBP1 filament assembly on mitochondria undefined
    • How ZBP1 discriminates between RIPK3 and MAVS signaling platforms not mechanistically resolved
  12. 2024 High

    Biophysical characterization revealed that ZBP1 Zα domains undergo concentration-dependent dimerization and liquid-liquid phase separation, while RHIM domains form amyloid-like fibrils that cross-polymerize with RIPK1 through a core IQIG motif; disruption of this motif abrogates necroptosis, providing a structural mechanism for RHIM-dependent signal amplification.

    Evidence DLS, SAXS, FRET, in vitro phase separation assays, amyloid fibril characterization, IQIG→AAAA mutagenesis, cell death assays

    PMID:38982083

    Open questions at the time
    • Whether phase separation occurs in vivo under physiological conditions not confirmed
    • High-resolution structure of ZBP1-RIPK1 RHIM heteromeric fibril not solved
  13. 2024 High

    Identification of a short ZBP1 splice isoform (ZBP1-S) that retains Zα domains but lacks RHIMs revealed an endogenous fine-tuning mechanism: ZBP1-S competitively sequesters Z-nucleic acid ligands away from full-length ZBP1, and its genetic ablation exacerbates ZBP1-driven skin inflammation.

    Evidence ZBP1-S-only knock-in mice, ZBP1-S knockout mice, competitive Z-NA binding assays, skin inflammation models; independently replicated by two simultaneous publications

    PMID:38748877 PMID:39300211

    Open questions at the time
    • Regulation of ZBP1-S vs ZBP1-L splicing ratio unknown
    • Whether ZBP1-S levels are modulated during infection or inflammation not tested
  14. 2025 High

    Host cell-encoded Z-RNAs, derived from endogenous retroelements in aberrantly extended 3' UTRs generated by viral disruption of transcription termination (DoTT), were identified as the major ZBP1-activating ligands during HSV-1 and IAV infection, fundamentally redefining ZBP1 as a sensor of virus-induced host transcriptome perturbation rather than of viral nucleic acids per se.

    Evidence eCLIP-seq mapping of Z-RNAs, viral mutants lacking CPSF inhibitors (ICP27, NS1), Z-RNA immunofluorescence, ectopic expression rescue, pharmacological CPSF blockade

    PMID:41082924

    Open questions at the time
    • Whether DoTT-generated Z-RNAs explain ZBP1 activation in non-viral inflammatory contexts unknown
    • Quantitative threshold of Z-RNA needed for ZBP1 activation not defined
  15. 2025 High

    STING was shown to transcriptionally upregulate both ZBP1 and MLKL and, upon combined caspase-8 deficiency and chronic STING activation, to drive Z-nucleic acid accumulation that triggers a ZBP1–RIPK1–RIPK3 necroptotic complex independent of FADD and TNFR1, linking STING gain-of-function disease (SAVI) to ZBP1-dependent pathology.

    Evidence Multiple conditional KO mice, co-IP of ZBP1-RIPK1-RIPK3 complex, SAVI mouse model (Sting1N153S), transcriptional analysis

    PMID:40834903

    Open questions at the time
    • Whether ZBP1-targeted therapy would benefit SAVI patients not tested clinically
    • Source and identity of Z-nucleic acids in STING-activated cells not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the high-resolution structure of full-length ZBP1 bound to Z-RNA in a signaling complex; how ZBP1 selects between RIPK3-dependent cell death, MAVS-dependent IFN, and cGAS-cooperative signaling; and the in vivo identity and tissue-specific repertoire of endogenous Z-nucleic acid ligands that calibrate ZBP1 activation thresholds in health and disease.
  • Full-length ZBP1 structure with Z-RNA ligand not solved
  • Decision logic between RIPK3 necroptosis vs. MAVS interferon vs. cGAS cooperation undefined
  • Tissue-specific endogenous Z-NA ligand repertoire not cataloged

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 5 GO:0060089 molecular transducer activity 5 GO:0140299 molecular sensor activity 5 GO:0003677 DNA binding 4
Localization
GO:0005829 cytosol 4 GO:0005739 mitochondrion 2 GO:0005634 nucleus 1
Pathway
R-HSA-168256 Immune System 11 R-HSA-5357801 Programmed Cell Death 10 R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 5
Partners
ADAR1CGASIRF3MAVSMLKLRIPK1RIPK3TBK1
Complex memberships
AIM2 PANoptosomeZBP1-RIPK3 necrosomeZBP1-cGAS-RIPK1-RIPK3 complex

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Crystal structure of the DLM-1 (ZBP1) Zα domain bound to left-handed Z-DNA at 1.85 Å resolution revealed a conserved winged-helix fold and a common Z-DNA recognition core shared with ADAR1 Zα, defining a family of Z-DNA binding proteins with a common structure-specific recognition mechanism. X-ray crystallography Nature structural biology High 11524677
2006 ZBP1 subcellular localization is controlled by its Zα domains: full-length ZBP1 shows finely punctate cytoplasmic distribution, while a splice variant lacking Zα1 (ΔZα1) accumulates in large cytoplasmic granules that are distinct from stress granules and processing bodies but dynamically interact with them. Full-length ZBP1 associates with stress granules upon heat shock, linking ZBP1 to mRNA sorting and metabolism. Fluorescence microscopy, circular dichroism spectroscopy, EMSA, live-cell imaging Nucleic acids research High 16990255
2007 ZBP1/DAI functions as a cytosolic DNA sensor that binds double-stranded DNA and, upon binding, enhances association with IRF3 and TBK1 to activate type I IFN genes. Three DNA-binding domains are required for full activation in vivo, and artificial dimerization of DAI results in DNA-independent IFN activation. RNA interference knockdown, overexpression, co-immunoprecipitation, reporter assays in mouse fibroblasts Nature High 17618271
2008 DAI/ZBP1 directly interacts with DNA in vitro and requires three DNA-binding domains for full in vivo activation of type I IFN. Artificially induced dimerization of DAI leads to DNA-independent activation of type I IFN genes, demonstrating that dimerization is a key step in DAI activation. In vitro DNA binding assays, forced dimerization constructs, reporter assays, RNAi Proceedings of the National Academy of Sciences of the United States of America High 18375758
2009 DAI/ZBP1 contains two RIP homotypic interaction motifs (RHIMs) that mediate NF-κB activation by recruiting the RHIM-containing kinases RIPK1 and RIPK3. Knockdown of either RIPK1 or RIPK3 impairs DAI-induced NF-κB activation. The MCMV protein M45 inhibits RIPK1/RIPK3 recruitment to DAI, blocking this signaling pathway. Co-immunoprecipitation, RNAi knockdown, NF-κB reporter assays, domain mapping EMBO reports High 19590578
2011 The Zβ domain of human DAI/ZBP1 binds to Z-DNA via a novel active B-Z transition mechanism: two Zβ proteins bind to B-DNA first, then convert it to left-handed Z-DNA — distinct from the Z-DNA binding mechanism of ADAR1 Zα. NMR spectroscopy, protein-DNA complex titration experiments FEBS letters High 21296080
2012 ZBP1/DAI forms a complex with RIPK3 via RHIM-dependent interactions to mediate virus-induced programmed necrosis during MCMV infection. DAI knockdown or knockout cells are resistant to virus-induced necrosis, and the MCMV-encoded vIRA protein targets the DAI-RIPK3 complex to suppress this death pathway. DAI acts analogously to the RIPK1-RIPK3 complex in death receptor-induced necroptosis but as the upstream RIPK3 partner in virus-induced necrosis. Genetic knockout/knockdown, co-immunoprecipitation, viral infection assays, in vivo mouse models Cell host & microbe High 22423968
2013 ZBP1/DAI functions as a DNA sensor in macrophages during self-DNA-induced lupus nephritis. ALD-DNA induces dimerization/oligomerization of DAI, which activates NF-κB and IRF3 signaling via calcium signaling, resulting in macrophage M2b polarization. Gain- and loss-of-function studies, in vivo DAI knockdown in macrophages, signaling pathway analysis The Journal of biological chemistry Medium 23553627
2016 RIPK1 prevents ZBP1-mediated necroptosis through its RHIM domain: the RIPK1 RHIM acts as a brake preventing ZBP1 from binding and activating RIPK3. Mutation of the RIPK1 RHIM (RIPK1mRHIM) causes perinatal lethality through ZBP1-RIPK3-MLKL-dependent necroptosis, and ZBP1 deficiency prevents this lethality. ZBP1 interacts strongly with phosphorylated RIPK3 in RIPK1mRHIM cells, demonstrating competitive RHIM engagement. Genetic knockin (RIPK1 RHIM mutant mice), knockout mice (ZBP1, RIPK3, MLKL), co-immunoprecipitation, in vivo mouse models Nature High 27819681 27819682
2016 ZBP1/DAI senses influenza A virus (IAV) proteins NP and PB1 to trigger cell death via the RIPK1-RIPK3-Caspase-8 axis. ZBP1 regulates NLRP3 inflammasome activation and induces apoptosis, necroptosis, and pyroptosis (PANoptosis) during IAV infection. ZBP1-deficient mice are protected from IAV mortality. Genetic knockout mice, co-immunoprecipitation, cell death assays, in vivo infection models Science immunology High 27917412
2017 MCMV-induced DAI/ZBP1-dependent necroptosis requires viral IE3-dependent early transcription from the viral genome, not input virion DNA or newly synthesized viral DNA. The Zα2 domain of DAI/ZBP1 is required for sensing the virus and triggering necroptosis, implicating viral RNA transcripts as the biologically relevant ligand. Viral mutant analysis, domain deletion constructs (Zα2), cell death assays EMBO reports High 28607035
2018 IRF1 is a transcriptional regulator of ZBP1 expression during influenza A virus infection. IRF1-deficient cells show reduced ZBP1 levels and consequently reduced NLRP3 inflammasome activation and cell death, placing IRF1 upstream of ZBP1 in the innate immune signaling cascade. IRF1 knockout cells, ChIP/transcriptional assays, inflammasome activation assays, cell death assays Journal of immunology Medium 29321274
2018 ZBP1/DAI senses nascent RNA transcripts (rather than viral DNA) during HSV1 infection to trigger necroptosis via RIPK3 and MLKL. ZBP1 acts as a pathogen sensor requiring elevated ZBP1 levels in human cells, and viral pathogenesis is restored in Zbp1-/-, Ripk3-/-, and Mlkl-/- mice, demonstrating epistatic pathway placement. Genetic knockout mice, viral mutant viruses (ICP6-deficient), species comparison (mouse vs human cells), in vivo infection models Cell death & disease High 30050136
2019 ZBP1 is required for both type I (IFN-β) and type II (IFN-γ) IFN-induced necroptosis. The N-terminal domain of ZBP1 mediates ZBP1-ZBP1 homointeraction, while its RHIM domain interacts with RIPK3 to initiate necroptosis. The anti-necroptotic function of RIPK1, FADD, and caspase-8 in IFN-treated cells is executed through caspase-8-mediated cleavage of RIPK3. Genetic knockout cell lines, domain truncation/mutation analysis, co-immunoprecipitation, cell death assays Cellular & molecular immunology High 31076724
2019 ZBP1/DAI drives IFN-stimulated RIPK3-mediated cell death (both caspase-8-dependent apoptosis and MLKL-dependent necroptosis) in settings of RIPK1 deficiency. IFN-activated JAK/STAT signaling induces ZBP1 expression, which then complexes with RIPK3 in the absence of RIPK1. Deletion of Zbp1 or core IFN signaling components prolongs viability of Ripk1-/- mice. Genetic knockout mice, co-immunoprecipitation, cell death assays, in vivo mouse survival studies Journal of immunology High 31358656
2020 Replicating influenza A virus (IAV) generates Z-RNAs that activate ZBP1 in the nucleus of infected cells. ZBP1 initiates RIPK3-mediated MLKL activation in the nucleus, causing nuclear envelope disruption, leakage of DNA into the cytosol, and eventual necroptosis ('inside-out' death pathway). Nuclear MLKL activation potently activates neutrophils. Z-RNA immunofluorescence, nuclear fractionation, RIPK3/MLKL genetic knockouts, confocal live-cell imaging, in vivo mouse models Cell High 32200799
2020 ZBP1 senses endogenous Z-form nucleic acids (Z-DNA/Z-RNA) via its Zα domains to trigger RIPK3-dependent necroptosis and inflammation in the absence of viral infection. Functional Zα domains are required for ZBP1-induced necroptosis in fibroblasts and for skin/intestinal inflammation in epithelium-specific RIPK1/FADD-deficient mice. ZBP1 constitutively binds cellular double-stranded RNA in a Zα-dependent manner, and complementary reads from endogenous retroelements are candidate Zα-domain ligands. Zα domain knock-in mice (disrupted nucleic acid binding), RIPK1/FADD conditional KO mice, ZBP1 KO mice, RNA immunoprecipitation, endogenous retroviral element RNA sequencing Nature High 32296175
2020 ZBP1 sensing of Z-RNA produced during influenza virus infection induces PANoptosis (pyroptosis, apoptosis, necroptosis) through assembly of a PANoptosome complex. A key step is ZBP1-NLRP3 inflammasome formation where ZBP1 recruits RIPK3 and caspase-8. Influenza viral proteins M2, NS1, and PB1-F2 modulate the ZBP1-NLRP3 inflammasome, and caspase-6 and type I IFN pathway are required for its assembly. Genetic knockout cells and mice, co-immunoprecipitation, inflammasome activation assays, cell death assays Immunological reviews Medium 32729116
2020 ZBP1 is the apical innate immune sensor of fungal infection (Candida albicans and Aspergillus fumigatus), required for inflammasome/pyroptosis, apoptosis, and necroptosis (PANoptosis) in response to fungal pathogens. The Zα2 domain of ZBP1 is required for inflammasome activation and PANoptosis during fungal infection. Genetic knockout cells, Zα2 domain-deletion constructs, cell death assays, inflammasome assays, fungal infection models The Journal of biological chemistry Medium 33109609
2021 ZBP1 promotes LPS-induced cell death and IL-1β release via constitutive binding to RIPK1. ZBP1-RIPK1 interaction is essential for initiating TRIFosome (TRIF-FADD-RIPK1-caspase-8 complex) assembly, caspase-8-mediated cell death, and inflammasome activation in response to Yersinia and LPS, positioning ZBP1 as an effector of TLR4/TRIF-dependent death signaling. Co-immunoprecipitation, genetic knockouts, cell death assays, bacterial infection models Nature communications Medium 33397971
2021 AIM2 regulates innate immune sensors pyrin and ZBP1 and drives PANoptosis during HSV1 and Francisella novicida infection via a large multi-protein complex (AIM2 PANoptosome) containing AIM2, pyrin, ZBP1, ASC, caspase-1, caspase-8, RIPK3, RIPK1, and FADD. Co-immunoprecipitation, genetic knockout mice and cells, cell death assays, in vivo infection models Nature High 34471287
2021 ADAR1 suppresses ZBP1-mediated PANoptosis by interacting with the Zα2 domain of ZBP1 to limit ZBP1-RIPK3 interactions. ZBP1 Zα2-domain deletion restores tumorigenesis in ADAR1-deficient mice, demonstrating the ADAR1-ZBP1 Zα2 axis regulates cell death and tumorigenesis. Co-immunoprecipitation (ADAR1-ZBP1 interaction), Zα2-domain knockout mice, in vivo tumor models, cell death assays Cell reports High 34686350
2021 Vaccinia virus E3 protein prevents ZBP1-mediated necroptosis by competing for Z-form RNA through its N-terminal Zα domain. In the absence of the E3 Zα domain, Z-form RNA accumulates during early VACV infection, triggering ZBP1 to recruit RIPK3 and execute necroptosis. The C-terminal dsRNA-binding domain of E3 must be retained to observe Z-form RNA accumulation. Viral Zα-domain deletion mutants, Z-RNA immunofluorescence, domain swap experiments, cell death assays Cell host & microbe High 34192517
2021 ZBP1-MLKL necroptotic signaling in irradiated tumor cells induces cytoplasmic DNA accumulation, autonomously activates cGAS-STING signaling, and creates a positive feedback loop between necroptosis and innate immune sensing to drive antitumor immunity. Ablation of caspase-8 enhanced STING pathway activation and antitumor effects. Genetic knockouts, cGAS-STING reporter assays, tumor irradiation models, immunofluorescence Science advances Medium 34613770
2022 ADAR1 mutation-driven pathology is fully rescued by ZBP1 ablation. ZBP1-dependent signaling (via RIPK3, caspase-8, and MLKL) underlies the autoinflammatory pathology caused by ADAR1 Zα-domain alteration, establishing ADAR1 as a negative regulator of sterile ZBP1 activation. Genetic knockout mice (ZBP1, RIPK3, MLKL, caspase-8), ADAR1 Zα mutant mice, disease phenotype rescue experiments Nature High 35859175 35859176 35859177
2022 ADAR1 prevents endogenous Z-RNA-dependent activation of ZBP1 by editing endogenous Alu element inverted-repeat dsRNAs. Loss of ADAR1 Zα function leads to ZBP1-driven caspase-8-dependent apoptosis and MLKL-mediated necroptosis. In Adar1mZα/- mice, ZBP1 promotes IFN activation and fatal pathology independently of RIPK1, RIPK3, MLKL, and caspase-8, suggesting a novel IFN-activating mechanism. Adar1 Zα-domain mutant knock-in mice, ZBP1 Zα mutant knock-in, ZBP1 KO, RIPK1/RIPK3/MLKL/casp8 KO epistasis, endogenous retroviral RNA sequencing Nature High 35859176
2022 ADAR1 depletion or mutation leads to accumulation of endogenous Z-RNAs (enriched in 3' UTRs of interferon-stimulated mRNAs) that activate ZBP1, culminating in RIPK3-mediated necroptosis in cancer cells. The small molecule curaxin CBL0137 directly activates ZBP1 by triggering Z-DNA formation in cells, inducing ZBP1-dependent necroptosis in cancer-associated fibroblasts and reversing ICB unresponsiveness. ADAR1 depletion, Z-RNA immunofluorescence, ZBP1 genetic knockout, chemical biology (CBL0137), in vivo tumor models Nature High 35614224
2022 ZBP1 induces cell-death-independent inflammatory signaling via K63- and M1-linked ubiquitin chains, dependent on RIPK1 and RIPK3 as scaffolds. Human ZBP1 associates with RIPK1, RIPK3, cIAP1, and LUBAC ubiquitin ligases to promote TAK1- and IKK-mediated inflammatory signaling and cytokine production independently of cell death. Caspase inhibition suppresses ZBP1-induced cell death but enhances cytokine production. Co-immunoprecipitation, ubiquitin chain linkage analysis, genetic knockouts, cytokine ELISA, inhibitor studies in human HT29 cells EMBO reports Medium 36268590
2022 Caspase-8 and FADD suppress spontaneous ZBP1-driven necroptosis through a positive feedback mechanism. FADD/caspase-8-deficient cells show dramatically increased ZBP1 expression, and spontaneous MLKL phosphorylation in vivo is dependent on ZBP1. ZBP1 expression and RIPK3/MLKL activation in caspase-8-deficient cells requires cGAS-STING-TBK1 signaling as a positive feedback loop. Genetic knockin mice (FLAG-MLKL), knockout mice (Casp8, ZBP1, cGAS, STING, TBK1), in vivo MLKL phosphorylation monitoring, western blotting Proceedings of the National Academy of Sciences of the United States of America High 36191211
2023 ZBP1 cooperates with cGAS to sense Z-form mitochondrial DNA. ZBP1 stabilizes Z-form mtDNA and nucleates a cytosolic complex containing cGAS, RIPK1, and RIPK3 to sustain STAT1 phosphorylation and type I IFN signaling. ZBP1-deficient mice are protected from doxorubicin-induced cardiotoxicity. Co-immunoprecipitation (ZBP1-cGAS-RIPK1-RIPK3 complex), Z-DNA immunofluorescence, ZBP1 knockout mice, doxorubicin cardiotoxicity model Cell High 37352855
2023 ZBP1 is induced during replicative crisis by the cGAS-STING pathway and reaches full activation when associated with TERRA (telomeric-repeat-containing RNA) from dysfunctional telomeres. TERRA-bound ZBP1 oligomerizes into filaments on the outer mitochondrial membrane, activating MAVS to launch a MAVS-dependent interferon response that drives crisis and tumor suppression. RNA immunoprecipitation (ZBP1-TERRA), super-resolution and electron microscopy of ZBP1 filaments on mitochondria, co-immunoprecipitation (ZBP1-MAVS), genetic knockout/knockdown Nature High 36755096
2023 ZBP1 is a critical regulator of the ZBP1-PANoptosome, activating NLRP3 inflammasome (for caspase-1, IL-1β, IL-18 maturation) and PANoptosis during IAV infection. The NLRP3 inflammasome is dispensable for cell death due to functional redundancies but critical for cytokine maturation. ZBP1-mediated PANoptosis is also central to the AIM2-PANoptosome during Francisella novicida and HSV1 infections. Genetic knockout macrophages and mice, inflammasome activation assays (IL-1β, IL-18 ELISA), cell death kinetics Current opinion in immunology Medium 37267644
2023 ZBP1 is constitutively expressed in multiple myeloma plasma cells and interacts with TBK1 and IRF3, leading to IRF3 phosphorylation. IRF3 then directly binds and activates cell cycle genes in cooperation with IRF4, promoting myeloma cell proliferation — a non-canonical function of ZBP1 independent of necroptosis. Co-immunoprecipitation (ZBP1-TBK1-IRF3), ChIP-seq (IRF3 binding to cell cycle genes), ZBP1 knockdown with proliferation assays, gene expression analysis Haematologica Medium 33596642
2023 TRIM32 is an E3 ubiquitin ligase that targets ZBP1 for proteasomal degradation. eCIRP (extracellular cold-inducible RNA-binding protein) competitively binds to ZBP1 and blocks the TRIM32-ZBP1 interaction, thereby stabilizing ZBP1 and enhancing ZBP1-RIPK3-dependent cell death in sepsis. Co-immunoprecipitation, ubiquitination assays, proteasome inhibitor experiments, competitive binding assays Military Medical Research Medium 39465383
2024 ZBP1 condensate formation facilitates Z-nucleic acid binding and antiviral signal transduction. The Zαβ domain dimerizes in a concentration-dependent manner, forming condensates with liquid-liquid phase separation properties in vitro and amyloid-like puncta in cells upon HSV and IAV infections. ZBP1 RHIM domains form typical amyloidal fibrils and cross-polymerize with RIPK1 through the core motif 206IQIG209, and mutation of this motif impedes necroptosis and antiviral immunity. DLS, SAXS, FRET, in vitro phase separation assays, amyloid fibril characterization, mutagenesis (IQIG→AAAA), cell death assays in HT-29 cells Cell death & disease High 38982083
2024 An alternatively spliced shorter isoform of ZBP1 (ZBP1-S), which contains Zα domains but lacks the RHIM domains, acts as an endogenous inhibitor of full-length ZBP1 (ZBP1-L) by competitively binding Z-nucleic acid ligands via its Zα domains. Mice and cells expressing only ZBP1-S are resistant to ZBP1-mediated cell death and inflammation. Loss of ZBP1-S accelerates and exacerbates ZBP1-mediated skin inflammation. ZBP1-S-only knock-in mice, ZBP1-S knockout mice, Z-nucleic acid competitive binding assays, cell death assays, skin inflammation models The EMBO journal High 38748877 39300211
2024 The RIPK1 death domain (DD) restrains ZBP1-mediated necroptosis: a DD mutation (R588E) disrupting DD-dependent oligomerization caused perinatal lethality from ZBP1-mediated necroptosis. Biochemical studies revealed that ZBP1-mediated RIPK3 activation requires RIPK1 kinase activity in wild-type cells but not in Ripk1R588E/R588E cells, suggesting that DD-dependent RIPK1 oligomerization and FADD interaction determine the mechanism of RIPK3 activation by ZBP1. Knock-in mice (RIPK1 R588E DD mutation), genetic epistasis (ZBP1 KO, RIPK3 KO), co-immunoprecipitation, kinase inhibitor studies Immunity High 38744293
2024 ZBP1 causes skin inflammation by triggering RIPK3-mediated necroptosis and RIPK1 kinase activity-independent but RHIM-dependent caspase-8-mediated apoptosis in keratinocytes. ZBP1-induced inflammatory cytokine production is completely prevented by combined inhibition of apoptosis and necroptosis, arguing against a cell death-independent pro-inflammatory ZBP1 function in keratinocytes. Constitutively active ZBP1 transgenic mice (C-terminally truncated ZBP1ca), RIPK3, MLKL, caspase-8 KO mice, RIPK1 kinase-dead knock-in, skin inflammation readouts Cell death and differentiation High 38849574
2024 ZBP1 senses mitochondrial Z-form DNA to activate RIPK3-dependent necroptosis and ferroptosis in endothelial cells. RIPK3 has a dual role: it phosphorylates MLKL to induce necroptosis and phosphorylates FSP1 to inhibit its enzymatic activity and promote ferroptosis. Specific deletion of Zbp1 or Ripk3 in endothelial cells simultaneously inhibits both necroptosis and ferroptosis. Endothelial cell-specific conditional KO mice (Zbp1, Ripk3, Mlkl), FSP1 phosphorylation assays, Z-DNA immunofluorescence, organelle damage readouts Cell death and differentiation High 38493248
2025 STING upregulates both ZBP1 and MLKL transcription, and combined caspase-8 deficiency and STING activation drives Z-nucleic acid accumulation that activates ZBP1 and triggers formation of a ZBP1-RIPK1-RIPK3 complex independently of the FADD-RIPK1-RIPK3 complex, executing necroptosis independently of TNFR1 and FADD. In SAVI patients, chronic STING activation orchestrates a necroptotic transcriptional program rescued by Ripk3 co-deletion. Genetic knockout/conditional KO mice (STING, ZBP1, RIPK3, FADD, TNFR1), co-immunoprecipitation (ZBP1-RIPK1-RIPK3 complex), SAVI mouse model (Sting1N153S), transcriptional analysis Nature High 40834903
2025 Host cell-encoded Z-RNAs (derived from endogenous retroelements in abnormally long 3' extensions of host mRNAs) are major and sufficient ZBP1-activating ligands during HSV-1 and IAV infection. Viral disruption of transcription termination (DoTT) via inhibition of CPSF-mediated 3' processing generates these aberrant host cell transcripts. Mutant viruses lacking ICP27 or NS1 (CPSF inhibitors) do not induce host Z-RNA accrual and are attenuated in ZBP1 stimulation. Z-RNA immunofluorescence, viral mutant viruses, eCLIP-seq mapping of Z-RNAs, ectopic ICP27/NS1 expression, CPSF pharmacological blockade, ZBP1 activation assays Nature High 41082924
2025 ZBP1 stabilizes UVB-induced cytosolic Z-DNA derived from oxidized mitochondrial DNA in keratinocytes, amplifying IFN production through cGAS-STING activation. ZBP1 knockdown abrogates UVB-induced IFN responses, and ZBP1 overexpression produces a lupus-like phenotype with spontaneous Z-DNA accumulation and IFN production. ZBP1 knockdown/overexpression in keratinocytes, Z-DNA immunofluorescence, cGAS-STING reporter assays, patient-derived lupus keratinocytes, UVB irradiation models Science immunology High 40053607

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2018 Recognition of RNA N6-methyladenosine by IGF2BP proteins enhances mRNA stability and translation. Nature cell biology 2381 29476152
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2007 DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response. Nature 1389 17618271
2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nature biotechnology 1336 16964243
2016 ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure. Cell 1233 26777405
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2012 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Molecular cell 973 22681889
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2016 ZBP1/DAI is an innate sensor of influenza virus triggering the NLRP3 inflammasome and programmed cell death pathways. Science immunology 691 27917412
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2012 DAI/ZBP1/DLM-1 complexes with RIP3 to mediate virus-induced programmed necrosis that is targeted by murine cytomegalovirus vIRA. Cell host & microbe 624 22423968
1999 A family of insulin-like growth factor II mRNA-binding proteins represses translation in late development. Molecular and cellular biology 610 9891060
2021 AIM2 forms a complex with pyrin and ZBP1 to drive PANoptosis and host defence. Nature 590 34471287
2019 ZBP1 and TAK1: Master Regulators of NLRP3 Inflammasome/Pyroptosis, Apoptosis, and Necroptosis (PAN-optosis). Frontiers in cellular and infection microbiology 581 31850239
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2005 Spatial regulation of beta-actin translation by Src-dependent phosphorylation of ZBP1. Nature 535 16306994
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
2021 circNDUFB2 inhibits non-small cell lung cancer progression via destabilizing IGF2BPs and activating anti-tumor immunity. Nature communications 478 33436560
2013 Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. Nature genetics 463 23535732
2020 Influenza Virus Z-RNAs Induce ZBP1-Mediated Necroptosis. Cell 455 32200799
2020 The regulation of the ZBP1-NLRP3 inflammasome and its implications in pyroptosis, apoptosis, and necroptosis (PANoptosis). Immunological reviews 451 32729116
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2010 Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science (New York, N.Y.) 421 20360068
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2011 IFIT1 is an antiviral protein that recognizes 5'-triphosphate RNA. Nature immunology 405 21642987
2020 Z-nucleic-acid sensing triggers ZBP1-dependent necroptosis and inflammation. Nature 386 32296175
2017 Synergistic drug combinations for cancer identified in a CRISPR screen for pairwise genetic interactions. Nature biotechnology 378 28319085
2007 Systematic analysis of the protein interaction network for the human transcription machinery reveals the identity of the 7SK capping enzyme. Molecular cell 367 17643375
2020 CircRNA-SORE mediates sorafenib resistance in hepatocellular carcinoma by stabilizing YBX1. Signal transduction and targeted therapy 366 33361760
2007 Functional specialization of beta-arrestin interactions revealed by proteomic analysis. Proceedings of the National Academy of Sciences of the United States of America 360 17620599
2016 RIPK1 counteracts ZBP1-mediated necroptosis to inhibit inflammation. Nature 353 27819681
2021 ADAR1 restricts ZBP1-mediated immune response and PANoptosis to promote tumorigenesis. Cell reports 345 34686350
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2016 RIPK1 inhibits ZBP1-driven necroptosis during development. Nature 338 27819682
2022 ADAR1 masks the cancer immunotherapeutic promise of ZBP1-driven necroptosis. Nature 318 35614224
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2009 DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB. EMBO reports 299 19590578
2022 ZBP1-dependent inflammatory cell death, PANoptosis, and cytokine storm disrupt IFN therapeutic efficacy during coronavirus infection. Science immunology 272 35587515
2008 Regulation of innate immune responses by DAI (DLM-1/ZBP1) and other DNA-sensing molecules. Proceedings of the National Academy of Sciences of the United States of America 264 18375758
2001 Structure of the DLM-1-Z-DNA complex reveals a conserved family of Z-DNA-binding proteins. Nature structural biology 262 11524677
2017 ZBP1: Innate Sensor Regulating Cell Death and Inflammation. Trends in immunology 228 29236673
2023 Cooperative sensing of mitochondrial DNA by ZBP1 and cGAS promotes cardiotoxicity. Cell 200 37352855
2022 ADAR1 prevents autoinflammation by suppressing spontaneous ZBP1 activation. Nature 199 35859175
2020 ZBP1 promotes fungi-induced inflammasome activation and pyroptosis, apoptosis, and necroptosis (PANoptosis). The Journal of biological chemistry 185 33109609
2022 ADAR1 mutation causes ZBP1-dependent immunopathology. Nature 170 35859177
2022 ADAR1 averts fatal type I interferon induction by ZBP1. Nature 167 35859176
2010 ZBP1 recognition of beta-actin zipcode induces RNA looping. Genes & development 161 20080952
2021 ZBP1-MLKL necroptotic signaling potentiates radiation-induced antitumor immunity via intratumoral STING pathway activation. Science advances 152 34613770
2019 ZBP1 mediates interferon-induced necroptosis. Cellular & molecular immunology 149 31076724
2011 Limited availability of ZBP1 restricts axonal mRNA localization and nerve regeneration capacity. The EMBO journal 134 21964071
2023 Telomere-to-mitochondria signalling by ZBP1 mediates replicative crisis. Nature 127 36755096
2021 Vaccinia virus E3 prevents sensing of Z-RNA to block ZBP1-dependent necroptosis. Cell host & microbe 115 34192517
2018 Species-independent contribution of ZBP1/DAI/DLM-1-triggered necroptosis in host defense against HSV1. Cell death & disease 112 30050136
2018 IRF1 Is a Transcriptional Regulator of ZBP1 Promoting NLRP3 Inflammasome Activation and Cell Death during Influenza Virus Infection. Journal of immunology (Baltimore, Md. : 1950) 109 29321274
2020 Sensing of endogenous nucleic acids by ZBP1 induces keratinocyte necroptosis and skin inflammation. The Journal of experimental medicine 106 32315377
2019 ZBP1/DAI Drives RIPK3-Mediated Cell Death Induced by IFNs in the Absence of RIPK1. Journal of immunology (Baltimore, Md. : 1950) 91 31358656
2023 PANoptosome signaling and therapeutic implications in infection: central role for ZBP1 to activate the inflammasome and PANoptosis. Current opinion in immunology 89 37267644
2021 ZBP1 promotes LPS-induced cell death and IL-1β release via RHIM-mediated interactions with RIPK1. Nature communications 85 33397971
2023 SARS-CoV-2 Z-RNA activates the ZBP1-RIPK3 pathway to promote virus-induced inflammatory responses. Cell research 84 36650286
2023 ZBP1 Protects Against mtDNA-Induced Myocardial Inflammation in Failing Hearts. Circulation research 84 36974722
2017 Murine cytomegalovirus IE3-dependent transcription is required for DAI/ZBP1-mediated necroptosis. EMBO reports 82 28607035
2023 Immune regulator IRF1 contributes to ZBP1-, AIM2-, RIPK1-, and NLRP12-PANoptosome activation and inflammatory cell death (PANoptosis). The Journal of biological chemistry 81 37557956
2023 ADAR1 and ZBP1 in innate immunity, cell death, and disease. Trends in immunology 75 36710220
2022 ZBP1: A Powerful Innate Immune Sensor and Double-Edged Sword in Host Immunity. International journal of molecular sciences 75 36142136
2006 ZBP1 subcellular localization and association with stress granules is controlled by its Z-DNA binding domains. Nucleic acids research 74 16990255
2022 Human ZBP1 induces cell death-independent inflammatory signaling via RIPK3 and RIPK1. EMBO reports 68 36268590
2021 Viral Z-RNA triggers ZBP1-dependent cell death. Current opinion in virology 68 34688984
2015 Specific interaction of KIF11 with ZBP1 regulates the transport of β-actin mRNA and cell motility. Journal of cell science 67 25588836
2024 Fn-OMV potentiates ZBP1-mediated PANoptosis triggered by oncolytic HSV-1 to fuel antitumor immunity. Nature communications 62 38693119
2022 Caspase-8 and FADD prevent spontaneous ZBP1 expression and necroptosis. Proceedings of the National Academy of Sciences of the United States of America 62 36191211
2013 DNA-dependent activator of interferon-regulatory factors (DAI) promotes lupus nephritis by activating the calcium pathway. The Journal of biological chemistry 58 23553627
2023 The Z-nucleic acid sensor ZBP1 in health and disease. The Journal of experimental medicine 57 37450010
2023 BPDE exposure promotes trophoblast cell pyroptosis and induces miscarriage by up-regulating lnc-HZ14/ZBP1/NLRP3 axis. Journal of hazardous materials 56 37167865
2024 Baicalin inhibits PANoptosis by blocking mitochondrial Z-DNA formation and ZBP1-PANoptosome assembly in macrophages. Acta pharmacologica Sinica 54 39223367
2024 Mechanism of lactic acidemia-promoted pulmonary endothelial cells death in sepsis: role for CIRP-ZBP1-PANoptosis pathway. Military Medical Research 54 39465383
2023 Bile acid-induced IRF3 phosphorylation mediates cell death, inflammatory responses, and fibrosis in cholestasis-induced liver and kidney injury via regulation of ZBP1. Hepatology (Baltimore, Md.) 53 37725754
2022 ZBP1-Mediated Necroptosis: Mechanisms and Therapeutic Implications. Molecules (Basel, Switzerland) 48 36615244
2017 Mechanism of β-actin mRNA Recognition by ZBP1. Cell reports 48 28147274
2024 ZBP1 causes inflammation by inducing RIPK3-mediated necroptosis and RIPK1 kinase activity-independent apoptosis. Cell death and differentiation 46 38849574
2012 RACK1 is a ribosome scaffold protein for β-actin mRNA/ZBP1 complex. PloS one 45 22523568
2024 Sensing of mitochondrial DNA by ZBP1 promotes RIPK3-mediated necroptosis and ferroptosis in response to diquat poisoning. Cell death and differentiation 44 38493248
2023 Recent advances in ZBP1-derived PANoptosis against viral infections. Frontiers in immunology 44 37261341
2023 ZBP1 Drives IAV-Induced NLRP3 Inflammasome Activation and Lytic Cell Death, PANoptosis, Independent of the Necroptosis Executioner MLKL. Viruses 43 38005819
2007 ZBP1 enhances cell polarity and reduces chemotaxis. Journal of cell science 42 17878234
2023 Triggering endogenous Z-RNA sensing for anti-tumor therapy through ZBP1-dependent necroptosis. Cell reports 41 37922310
2024 The RIPK1 death domain restrains ZBP1- and TRIF-mediated cell death and inflammation. Immunity 40 38744293
2024 ZBP1-mediated apoptosis and inflammation exacerbate steatotic liver ischemia/reperfusion injury. The Journal of clinical investigation 37 38743492
2022 The innate sensor ZBP1-IRF3 axis regulates cell proliferation in multiple myeloma. Haematologica 35 33596642
2019 Influenza Virus Infection Induces ZBP1 Expression and Necroptosis in Mouse Lungs. Frontiers in cellular and infection microbiology 34 31440477
2020 ZBP1 (DAI/DLM-1) promotes osteogenic differentiation while inhibiting adipogenic differentiation in mesenchymal stem cells through a positive feedback loop of Wnt/β-catenin signaling. Bone research 33 32195010
2022 Fisetin-induced cell death in human ovarian cancer cell lines via zbp1-mediated necroptosis. Journal of ovarian research 32 35538559
2023 Necroptosis of macrophage is a key pathological feature in biliary atresia via GDCA/S1PR2/ZBP1/p-MLKL axis. Cell death & disease 30 36859525
2025 Epidermal ZBP1 stabilizes mitochondrial Z-DNA to drive UV-induced IFN signaling in autoimmune photosensitivity. Science immunology 28 40053607
2024 TRIM56 Modulates YBX1 Degradation to Ameliorate ZBP1-Mediated Neuronal PANoptosis in Spinal Cord Injury. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 27 39291396
2024 Sensing of endogenous retroviruses-derived RNA by ZBP1 triggers PANoptosis in DNA damage and contributes to toxic side effects of chemotherapy. Cell death & disease 24 39465258
2019 Necroptosis in pulmonary macrophages mediates lipopolysaccharide-induced lung inflammatory injury by activating ZBP-1. International immunopharmacology 24 31655343
2024 ZBP1 and TRIF trigger lethal necroptosis in mice lacking caspase-8 and TNFR1. Cell death and differentiation 23 38548850
2025 SARS-CoV-2 infection induces ZBP1-dependent PANoptosis in bystander cells. Proceedings of the National Academy of Sciences of the United States of America 20 40627395
2023 PTRF-IL33-ZBP1 signaling mediating macrophage necroptosis contributes to HDM-induced airway inflammation. Cell death & disease 20 37454215
2025 Targeted Degradation of ZBP1 with Covalent PROTACs for Anti-Inflammatory Treatment of Infections. Angewandte Chemie (International ed. in English) 19 40013409
2024 ZBP1 promotes hepatocyte pyroptosis in acute liver injury by regulating the PGAM5/ROS pathway. Annals of hepatology 18 38331384
2023 ZBP1/DAI-Dependent Cell Death Pathways in Influenza A Virus Immunity and Pathogenesis. Current topics in microbiology and immunology 18 31970498
2024 Apoptosis dysfunction: unravelling the interplay between ZBP1 activation and viral invasion in innate immune responses. Cell communication and signaling : CCS 17 38402193
2024 ZBP1 condensate formation synergizes Z-NAs recognition and signal transduction. Cell death & disease 17 38982083
2024 IRF1 regulation of ZBP1 links mitochondrial DNA and chondrocyte damage in osteoarthritis. Cell communication and signaling : CCS 16 39026271
2025 STING induces ZBP1-mediated necroptosis independently of TNFR1 and FADD. Nature 15 40834903
2011 The Zβ domain of human DAI binds to Z-DNA via a novel B-Z transition pathway. FEBS letters 15 21296080
2025 Z-Nucleic Acid Sensing and Activation of ZBP1 in Cellular Physiology and Disease Pathogenesis. Immunological reviews 14 39748135
2024 Lipolysis engages CD36 to promote ZBP1-mediated necroptosis-impairing lung regeneration in COPD. Cell reports. Medicine 14 39255796
2024 Decoding the multiple functions of ZBP1 in the mechanism of sepsis-induced acute lung injury. Communications biology 14 39433574
2024 Quercetin Protects against Silicon dioxide Particles-induced spleen ZBP1-Mediated PANoptosis by regulating the Nrf2/Drp1/mtDNA axis. International immunopharmacology 14 39488923
2018 Prevalence and Molecular Study of G6PD Deficiency in the Dai and Jingpo Ethnic Groups in the Dehong Prefecture of the Yunnan Province. Human heredity 14 29860254
2024 ASFV infection induces macrophage necroptosis and releases proinflammatory cytokine by ZBP1-RIPK3-MLKL necrosome activation. Frontiers in microbiology 13 38952452
2024 A shorter splicing isoform antagonizes ZBP1 to modulate cell death and inflammatory responses. The EMBO journal 13 39300211
2025 ZBP1 senses Brucella abortus DNA triggering type I interferon signaling pathway and unfolded protein response activation. Frontiers in immunology 12 39850894
2025 ZBP1-mediated PANoptosis is a crucial lethal form in diverse keratinocyte death modalities in UVB-induced skin injury. Cell death & disease 12 39863598
2025 Host cell Z-RNAs activate ZBP1 during virus infections. Nature 12 41082924
2024 Z-nucleic acid sensor ZBP1 in sterile inflammation. Clinical immunology (Orlando, Fla.) 12 38346464
2024 Inflammatory cell death PANoptosis is induced by the anti-cancer curaxin CBL0137 via eliciting the assembly of ZBP1-associated PANoptosome. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 12 38353723
2024 Elabela ameliorates neuronal pyroptosis and mitochondrial fission via APJ/ZBP1 signaling in ischemic stroke. Experimental neurology 12 38679280
2024 A ZBP1 isoform blocks ZBP1-mediated cell death. Cell reports 12 38748877
2023 ZBP1 and heatstroke. Frontiers in immunology 12 36845119
2025 Inhibition of Zbp1-PANoptosome-mediated PANoptosis effectively attenuates acute pancreatitis. Cell death discovery 11 40240343
2024 Regulation of Zbp1 by miR-99b-5p in microglia controls the development of schizophrenia-like symptoms in mice. The EMBO journal 11 38528182