Affinage

ZBP1

Z-DNA-binding protein 1 · UniProt Q9H171

Length
429 aa
Mass
46.3 kDa
Annotated
2026-06-11
100 papers in source corpus 42 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ZBP1 (DAI/DLM-1) is an interferon-inducible innate immune sensor that detects Z-form nucleic acids through its N-terminal Zα domains and converts this recognition into RHIM-dependent activation of cell death and inflammatory signaling (PMID:17618271, PMID:11524677, PMID:28716805). Structural work defined the Zα winged-helix fold that recognizes left-handed Z-DNA via a structure-specific core shared with ADAR1 (PMID:11524677), and ZBP1 binds both Z-DNA and Z-RNA, with Zα1/Zα2 mutations abolishing ligand engagement and downstream cell death (PMID:28716805, PMID:28607035). Ligand binding drives ZBP1 oligomerization—self-association via its N-terminal/Zαβ region and condensate/amyloid-like assembly—as the activating step (PMID:18375758, PMID:31076724, PMID:38982083). Activated ZBP1 uses its two RHIM domains to recruit RIPK3 and RIPK1, nucleating signaling that drives PANoptosis: RIPK3-MLKL necroptosis, RIPK1-caspase-8 apoptosis, and inflammasome-linked pyroptosis, alongside NF-κB- and IRF3-dependent inflammation (PMID:19590578, PMID:27746097, PMID:31358656, PMID:38849574). This pathway senses viral Z-RNAs during IAV, MCMV, HSV-1, and vaccinia infection (PMID:22423968, PMID:27746097, PMID:28607035, PMID:34192517), and the relevant ligands include host cell-encoded Z-RNAs from endogenous retroelements in aberrant transcripts generated when viruses disrupt transcription termination (PMID:41082924); influenza-induced nuclear Z-RNA can drive 'inside-out' nuclear necroptosis with nuclear-envelope disruption (PMID:32200799). ZBP1 signaling is restrained at multiple levels: RIPK1's RHIM and death domain compete for RIPK3 to prevent constitutive activation (PMID:27819681, PMID:27819682, PMID:38744293), ADAR1 edits endogenous dsRNA and directly binds the Zα2 domain to block ZBP1-RIPK3 engagement (PMID:34686350, PMID:35859175, PMID:35859177, PMID:35859176), caspase-8/FADD suppress spontaneous ZBP1 expression (PMID:36191211), and a short RHIM-lacking isoform competes for Z-nucleic acid binding (PMID:39300211). Beyond infection, ZBP1 senses Z-form mitochondrial DNA to nucleate a cGAS-RIPK1-RIPK3 complex that sustains type I IFN signaling and contributes to doxorubicin cardiotoxicity, and a crisis-associated isoform binds TERRA to activate MAVS on mitochondria (PMID:37352855, PMID:36755096). Separately, the same gene product functions as zipcode-binding protein 1 in β-actin mRNA localization, where its KH3-KH4 di-domain recognizes the actin zipcode to control cell polarity and motility (PMID:28147274, PMID:17878234). Human ZBP1 is not required for cytosolic DNA-induced IFN-β responses in human cells, distinguishing it from the mouse DNA-sensor role (PMID:18771559).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 2001 High

    Established the structural basis of Z-nucleic acid recognition, defining the Zα domain fold that would later explain ZBP1 ligand specificity.

    Evidence X-ray crystallography of the DLM-1/ZBP1 Zα domain bound to Z-DNA

    PMID:11524677

    Open questions at the time
    • Did not address full-length protein assembly
    • No downstream signaling function defined at this stage
  2. 2007 High

    Identified ZBP1 as a cytosolic DNA sensor that activates type I IFN, answering what links cytosolic DNA to the IRF3-TBK1 axis.

    Evidence siRNA knockdown, Co-IP, and reporter assays in mouse fibroblasts

    PMID:17618271

    Open questions at the time
    • Did not resolve whether B-DNA or Z-DNA is the physiological ligand
    • Did not establish redundancy with other DNA sensors
  3. 2007 Medium

    Defined a distinct mRNA-localization function of the same gene product (zipcode-binding protein 1) in controlling β-actin mRNA targeting and cell motility.

    Evidence Overexpression, mRNA localization imaging, chemotaxis and in vivo tumor imaging in metastatic cells

    PMID:17878234

    Open questions at the time
    • Relationship between RNA-localization and immune-sensor functions unresolved
    • Single-cell-type system
  4. 2008 High

    Showed that dimerization is the key activation step and that multiple DNA-binding domains are required, framing oligomerization as the trigger for signaling.

    Evidence Domain mutagenesis and forced-dimerization constructs with reporter assays

    PMID:18375758

    Open questions at the time
    • Did not define the physiological dimerization trigger
    • Mechanism of RHIM engagement not yet shown
  5. 2008 Medium

    Tested whether the DNA-sensor role generalizes to human cells and found it does not, revealing a species-specific limitation of the IFN-sensor function.

    Evidence siRNA knockdown and overexpression with IFN-β readouts in human A549 cells vs mouse cells

    PMID:18771559

    Open questions at the time
    • Negative result does not exclude other human ZBP1 functions
    • Did not assess Z-RNA or cell-death roles in human cells
  6. 2009 High

    Connected ZBP1 to RHIM-dependent kinase recruitment, showing it relays signals to RIPK1/RIPK3 and is targeted by viral RHIM mimics.

    Evidence Co-IP, siRNA knockdown of RIPK1/RIPK3, NF-κB reporter assays, MCMV M45 analysis

    PMID:19590578

    Open questions at the time
    • Cell-death versus NF-κB branching not resolved
    • Did not establish in vivo relevance
  7. 2012 High

    Demonstrated that ZBP1-RIPK3 complexes drive virus-induced programmed necrosis in vivo, establishing the necroptotic arm of ZBP1 signaling.

    Evidence Co-IP, Zbp1−/− mouse genetics, MCMV pathogenesis and viral vIRA evasion

    PMID:22423968

    Open questions at the time
    • Did not identify the activating viral ligand
    • MLKL involvement not yet shown
  8. 2016 High

    Extended ZBP1 sensing to RNA viruses, showing IAV vRNP detection drives RIPK3-mediated necroptosis and apoptosis.

    Evidence Zbp1 KO/KD cells and mice, RIPK3 Co-IP, cell death assays

    PMID:27746097

    Open questions at the time
    • Did not define the Z-RNA nature of the ligand
    • Upstream priming requirements unclear
  9. 2016 High

    Revealed RIPK1's RHIM as a brake on ZBP1, explaining how ZBP1-RIPK3 necroptosis is held in check during development.

    Evidence Ripk1 RHIM knock-in mice, Co-IP of ZBP1-RIPK3, Zbp1−/− rescue, pRIPK3 blots

    PMID:27819681 PMID:27819682

    Open questions at the time
    • Did not define the endogenous activating ligand in this setting
    • Mechanism of RHIM competition at structural level unresolved
  10. 2017 High

    Identified Z-RNA as the activating ligand by showing Zα mutations abolish necroptosis and that viral transcription, not DNA replication, is required.

    Evidence Zα domain knock-in mutants, MCMV infection assays, RNA cross-linking, viral mutants

    PMID:28607035 PMID:28716805

    Open questions at the time
    • Precise Z-RNA species not mapped
    • Did not address host versus viral RNA origin
  11. 2017 Medium

    Clarified ZBP1 domain architecture for activation and upstream priming, mapping self-interaction to the N-terminus and showing RIG-I-MAVS-IFN dependence and ZBP1 ubiquitination.

    Evidence Domain deletion Co-IP, RIG-I/MAVS KO cells, ubiquitination and vRNP pulldown assays

    PMID:28634194 PMID:31076724

    Open questions at the time
    • Ubiquitin ligase not identified at this stage
    • Single-lab studies
  12. 2019 High

    Showed ZBP1-RIPK3 can act independently of RIPK1 downstream of IFN and can restrict viruses via immunometabolism rather than death, broadening outcome diversity.

    Evidence Zbp1−/− in Ripk1−/− background, JAK/STAT inhibition; ZIKV neuron model with metabolomics and IRG1/itaconate analysis

    PMID:30635240 PMID:31358656

    Open questions at the time
    • Determinants selecting death versus metabolic restriction unclear
    • Cell-type specificity of outcomes not resolved
  13. 2020 High

    Demonstrated nuclear ZBP1 signaling and sterile activation by endogenous Z-nucleic acids, establishing ZBP1 as a sensor of self retroelement-derived dsRNA.

    Evidence IAV Z-RNA detection, nuclear RIPK3/MLKL imaging, multiple Ripk1/FADD mutant mice with Zbp1−/− rescue, nuclear export inhibition, RNA cross-linking

    PMID:32200799 PMID:32296175

    Open questions at the time
    • Identity of specific endogenous retroelement transcripts incomplete
    • Trigger that overcomes normal suppression in disease not fully defined
  14. 2021 High

    Established ADAR1 as a direct negative regulator binding the Zα2 domain to block ZBP1-RIPK3 engagement and PANoptosis.

    Evidence ADAR1-ZBP1 Co-IP, Zα2 deletion knock-in mice, conditional ADAR1 KO, tumor and PANoptosis assays

    PMID:34686350

    Open questions at the time
    • Whether suppression is purely editing-dependent or also via direct binding not fully separated
    • Structural basis of ADAR1-Zα2 contact unresolved
  15. 2021 Medium

    Placed ZBP1 within larger inflammatory-death complexes and TRIF/RIPK1 pathways, showing constitutive RIPK1 binding and incorporation into AIM2-containing PANoptosomes.

    Evidence ZBP1-RIPK1 Co-IP and KO in LPS/Yersinia models; multi-protein PANoptosome Co-IP with AIM2/pyrin KO in HSV-1/F. novicida infection

    PMID:33397971 PMID:34471287

    Open questions at the time
    • Stoichiometry and assembly order of the PANoptosome unresolved
    • Whether ZBP1-RIPK1 binding is ligand-dependent unclear
  16. 2021 High

    Defined viral evasion by Zα competition, showing vaccinia E3 sequesters Z-RNA via its own Zα domain to block ZBP1 necroptosis.

    Evidence E3 Zα mutant VACV, Z-RNA detection, ZBP1/RIPK3/MLKL KO cells, Zα domain swaps

    PMID:34192517

    Open questions at the time
    • Quantitative ligand competition not measured
    • Generalizability across poxviruses untested
  17. 2022 High

    Confirmed and extended the ADAR1-ZBP1 axis, showing Alu-derived Z-RNA accumulation upon loss of ADAR1's Zα domain drives ZBP1-dependent death, fully rescued by ZBP1 ablation.

    Evidence Adar1 Zα-mutant and KO mice with Zbp1−/− rescue, cell death readouts, Alu RNA-seq; CBL0137 Z-DNA induction in fibroblasts

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

    Open questions at the time
    • Therapeutic window of pharmacologic ZBP1 activation undefined
    • Tissue-specific contributions of editing loss incomplete
  18. 2022 Medium

    Defined cell-death-independent inflammatory signaling, showing ZBP1 scaffolds RIPK1/RIPK3-dependent ubiquitination and TLR3/4 inflammatory amplification.

    Evidence Co-IP of ZBP1-RIPK1-RIPK3-cIAP1-LUBAC, ubiquitin pulldowns, kinase-dead mutants in human cells; ZBP1-RIPK1-TRIF Co-IP and LPS sepsis mouse model

    PMID:35666872 PMID:36268590

    Open questions at the time
    • Relative contribution of scaffolding versus death signaling in vivo unclear
    • Single-lab human/mouse systems
  19. 2022 High

    Showed caspase-8/FADD suppress spontaneous ZBP1 expression via a cGAS-STING-TBK1 feedback loop, defining a transcriptional brake on sterile ZBP1 necroptosis.

    Evidence Casp8−/− and FADD−/− mice with Zbp1−/− rescue, FLAG-MLKL knock-in reporter, cGAS/STING/TBK1 inhibition

    PMID:36191211

    Open questions at the time
    • Direct transcriptional regulators of Zbp1 not mapped
    • Ligand driving spontaneous activation undefined
  20. 2023 High

    Extended ZBP1 sensing to mitochondrial Z-DNA and TERRA, revealing it nucleates cGAS-RIPK or MAVS complexes to sustain IFN and drive crisis or cardiotoxicity.

    Evidence ZBP1 KO mice, Z-DNA detection, ZBP1-cGAS-RIPK Co-IP, STAT1 phosphorylation, doxorubicin model; crisis isoform TERRA binding, mitochondrial imaging, MAVS Co-IP, oligomerization assays

    PMID:36755096 PMID:37352855

    Open questions at the time
    • How Z-DNA stabilization on mtDNA is regulated unclear
    • Isoform-specific localization determinants incomplete
  21. 2024 Medium

    Resolved the molecular basis of RIPK1's restraint and the biophysics of ZBP1 assembly, defining RHIM amyloid cross-polymerization and condensate formation as activation steps.

    Evidence Ripk1 R588E DD knock-in mice; DLS/SAXS, in vitro condensate and amyloid assays, RHIM mutagenesis with necroptosis readout

    PMID:38744293 PMID:38982083

    Open questions at the time
    • High-resolution structure of the activated ZBP1-RIPK3 fibril lacking
    • In vivo relevance of phase separation untested
  22. 2024 High

    Dissected ZBP1-driven inflammatory disease, showing it executes both necroptosis and kinase-independent RIPK1-caspase-8 apoptosis, with STING upregulating ZBP1 and forming a FADD-independent ZBP1-RIPK1-RIPK3 complex in dermatitis.

    Evidence ZBP1ca transgenic and Casp8E-KO mice with MLKL/caspase-8/STING/RIPK3 deletions, Co-IP, SAVI model rescue, RIPK1 kinase-dead knock-in

    PMID:38849574 PMID:40834903

    Open questions at the time
    • Endogenous triggers in human SAVI not fully defined
    • Balance between necroptotic and apoptotic arms across tissues unresolved
  23. 2024 Medium

    Identified endogenous regulators of ZBP1: a short RHIM-lacking isoform that competes for Z-RNA, and ligand-independent activation via aggregation and degradation control.

    Evidence ZBP1-S knock-in and KO mice, isoform combination death assays; steatotic liver I/R model with ZBP1 aggregation; TRIM32/CIRP ubiquitination and Co-IP in sepsis

    PMID:38743492 PMID:39300211 PMID:39465383

    Open questions at the time
    • Regulation of isoform splicing ratio in disease unclear
    • Whether ROS-induced aggregation uses the same RHIM interface as Z-nucleic acid sensing unresolved
  24. 2025 High

    Pinpointed host-encoded retroelement Z-RNAs—generated by virus-driven disruption of transcription termination—as the major sufficient ZBP1 ligands during HSV-1 and IAV infection.

    Evidence Z-RNA sequencing, ICP27/NS1 viral mutants and ectopic expression, CPSF blockade, ZBP1 KO controls

    PMID:41082924

    Open questions at the time
    • Whether all ZBP1-activating contexts share this host-RNA origin unknown
    • Structural definition of these Z-RNAs at the Zα interface lacking

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse ZBP1 ligands (viral and host Z-RNA, mitochondrial Z-DNA, TERRA, stress-induced aggregation) are integrated to select between necroptosis, apoptosis, pyroptosis, metabolic restriction, and IFN output remains unresolved.
  • No unifying structural model of activated ZBP1 signaling complexes
  • Determinants of outcome selection across cell types undefined
  • Human-specific ZBP1 functions versus mouse remain incompletely mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 5 GO:0003677 DNA binding 4 GO:0060089 molecular transducer activity 3 GO:0060090 molecular adaptor activity 3 GO:0140299 molecular sensor activity 3
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 2 GO:0005739 mitochondrion 2
Pathway
R-HSA-168256 Immune System 5 R-HSA-5357801 Programmed Cell Death 5 R-HSA-8953854 Metabolism of RNA 2
Partners
ADAR1AIM2CGASCIRPMAVSRIPK1RIPK3TRIM32
Complex memberships
AIM2-ZBP1 PANoptosomeTRIFosome (FADD-RIPK1-caspase-8)ZBP1-RIPK3 necroptosomeZBP1-cGAS-RIPK1-RIPK3 mitochondrial complex

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 ZBP1/DAI (DLM-1) binds double-stranded DNA directly and, upon binding, enhances its association with IRF3 transcription factor and TBK1 serine/threonine kinase to activate type I interferon gene expression. siRNA knockdown of ZBP1 inhibited DNA-mediated innate immune gene induction, establishing ZBP1 as a cytosolic DNA sensor upstream of the IRF3-TBK1 axis. siRNA knockdown, co-immunoprecipitation, overexpression in mouse fibroblasts, reporter assays Nature High 17618271
2001 Crystal structure of the DLM-1 (ZBP1) Zα domain bound to left-handed Z-DNA at 1.85 Å resolution revealed a winged-helix fold and a conserved 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
2008 ZBP1/DAI requires three DNA-binding domains (Zα1, Zα2, and D3) for full activation of type I IFN in vivo; artificially induced dimerization of DAI causes DNA-independent activation of type I IFN genes, indicating dimerization is a key step in DAI activation. Mutational analysis of DNA-binding domains, forced dimerization constructs, reporter assays, in vitro DNA binding Proceedings of the National Academy of Sciences of the United States of America High 18375758
2009 ZBP1/DAI contains two RIP homotypic interaction motifs (RHIMs) that recruit RHIM-containing kinases RIPK1 and RIPK3 to relay NF-κB activation signals downstream of cytosolic DNA sensing. RIPK3 knockdown, like RIPK1 knockdown, reduces DAI-induced NF-κB activation. The MCMV protein M45 inhibits RIP recruitment to DAI via its own RHIM domain. Co-immunoprecipitation, siRNA knockdown of RIPK1/RIPK3, NF-κB reporter assays, RHIM domain identification by sequence analysis EMBO reports High 19590578
2012 ZBP1/DAI forms a complex with RIPK3 via RHIM-dependent interactions to mediate virus-induced programmed necrosis during MCMV infection. DAI-deficient cells and mice are resistant to MCMV-induced necrosis, and the MCMV vIRA protein suppresses this pathway by targeting the DAI-RIP3 complex. Co-immunoprecipitation, DAI knockdown/knockout cells, Zbp1−/− mouse genetics, viral pathogenesis assays Cell host & microbe High 22423968
2016 ZBP1 senses influenza A virus genomic RNA (vRNPs) and associates with RIPK3, recruiting MLKL and RIPK1 to RIPK3 to trigger both necroptosis and apoptosis. DAI-deficient cells and mice fail to activate RIPK3 in response to IAV, establishing DAI as the link between IAV RNA and RIPK3 activation. DAI knockout/knockdown cells, RIPK3 co-immunoprecipitation, cell death assays, Zbp1−/− mouse infection model Cell host & microbe High 27746097
2016 RIPK1's RHIM domain prevents ZBP1 from binding and activating RIPK3; mutation of RIPK1 RHIM (IQIG→AAAA) allows ZBP1 to interact with phosphorylated RIPK3, causing ZBP1-RIPK3-MLKL-dependent necroptosis and perinatal lethality. ZBP1 deficiency prevents necroptosis and skin inflammation in RIPK1-RHIM-mutant and epidermis-specific RIPK1-KO mice. RHIM knock-in mouse genetics, Co-immunoprecipitation, Zbp1−/− mouse genetics, histopathology Nature High 27819681 27819682
2016 The RIPK1 RHIM acts as a brake preventing ZBP1 from engaging RIPK3's RHIM; in RIPK1-RHIM mutant (IQIG→AAAA) mice, ZBP1 constitutively interacts with RIPK3 (but not in WT or RIPK3-RHIM mutant cells), driving RIPK3 autophosphorylation (Thr231/Ser232) and MLKL-dependent perinatal lethality. Knock-in mouse genetics (Ripk1RHIM/RHIM), Co-immunoprecipitation of ZBP1-RIPK3, Zbp1−/− genetic rescue, Western blot for pRIPK3 Nature High 27819682
2017 ZBP1 directly binds RNA via its Zα domains; mutation of key amino acids in Zα1 and Zα2 required for Z-nucleic acid binding abolished ZBP1-mediated necroptosis during MCMV infection and upon ZBP1 overexpression. Cell death required RNA synthesis but not viral DNA replication, implicating Z-RNA as the ZBP1 ligand. Reconstitution/knock-in models with ZBP1 Zα domain mutations, MCMV infection cell death assays, RNA cross-linking, viral replication inhibitor experiments The EMBO journal High 28716805
2017 ZBP1 activation during IAV infection requires upstream RIG-I-MAVS-IFN-β signaling; ZBP1 undergoes ubiquitination after IAV infection as a post-translational modification. ZBP1 senses IAV vRNP complexes (not free RNA) to trigger programmed cell death. RIG-I/MAVS KO cells, IFN-β signaling inhibition, ubiquitination assays, vRNP pulldown, cell death assays The Journal of experimental medicine Medium 28634194
2017 The N-terminal domain of ZBP1 mediates ZBP1-ZBP1 homointeraction, and the RHIM domain in the C-terminal region interacts with RIPK3 to initiate RIPK3-dependent necroptosis downstream of IFN stimulation. Domain deletion constructs, co-immunoprecipitation of ZBP1 self-interaction and ZBP1-RIPK3, IFN-induced necroptosis assays in RIPK1/FADD/caspase-8 KO cells Cellular & molecular immunology Medium 31076724
2017 MCMV requires viral IE3-dependent early transcription (not input virion DNA or newly synthesized viral DNA) for DAI/ZBP1-mediated necroptosis; the Zα2 domain of DAI/ZBP1 is required for sensing MCMV and triggering necroptosis, implicating viral RNA transcripts as the relevant ligand. Viral mutants blocking DNA replication/IE3 transcription, Zα2 domain mutation of ZBP1, necroptosis assays EMBO reports Medium 28607035
2019 ZBP1 and RIPK3 activation in ZIKV-infected neurons does not induce necroptosis but instead restricts viral replication by upregulating the enzyme IRG1, leading to itaconate production that inhibits succinate dehydrogenase and suppresses viral genome replication via an immunometabolic mechanism. ZBP1/RIPK3 KO murine neurons, ZIKV infection model, metabolomics, IRG1 KO, itaconate supplementation Immunity High 30635240
2019 ZBP1/DAI drives RIPK3-mediated cell death (necroptosis and apoptosis) in response to IFNs in the absence of RIPK1; IFN-activated JAK/STAT signaling induces ZBP1 expression, which then complexes with RIPK3 to trigger caspase-8-mediated apoptosis and MLKL-driven necroptosis. Zbp1−/− genetics in Ripk1−/− background, JAK/STAT inhibitors, ZBP1-RIPK3 co-immunoprecipitation, Ripk1−/− mouse survival studies Journal of immunology Medium 31358656
2020 Replicating influenza A virus generates Z-RNAs that activate ZBP1 in the nucleus of infected cells; nuclear ZBP1 then initiates RIPK3-mediated MLKL activation in the nucleus, causing nuclear envelope disruption, DNA leakage into cytosol, and 'inside-out' necroptosis. Nuclear MLKL activation potently activates neutrophils. Z-RNA detection in IAV-infected cells, RIPK3/MLKL nuclear localization by imaging, MLKL-deficient mice, neutrophil recruitment assays, survival studies Cell High 32200799
2020 Zα-domain-dependent sensing of endogenous Z-form nucleic acids (Z-DNA/Z-RNA) by ZBP1 triggers RIPK3-dependent necroptosis and inflammation in the absence of viral infection. ZBP1 constitutively binds cellular double-stranded RNA in a Zα-dependent manner; inhibition of nuclear export triggers Zα-dependent RIPK3 activation in the nucleus. Endogenous retroelement-derived dsRNA is implicated as a Zα-domain ligand. Ripk1mR/mR and RIPK1E-KO and FADDIEC-KO mouse models with Zbp1−/− genetic rescue, nuclear export inhibition, Zα domain mutagenesis, ZBP1 RNA cross-linking Nature High 32296175
2021 ADAR1 interacts with the Zα2 domain of ZBP1 to suppress ZBP1-RIPK3 interactions and thereby limit ZBP1-mediated PANoptosis. Deletion of ADAR1 (Adar1fl/fl LysMcre) increases ZBP1-dependent cell death; deletion of the ZBP1 Zα2 domain restores tumorigenesis in ADAR1-deficient mice, demonstrating ADAR1 acts as a negative regulator of ZBP1 via Zα2-domain interaction. Co-immunoprecipitation of ADAR1-ZBP1, Zα2 domain deletion knock-in mice, conditional ADAR1 KO, tumor models, PANoptosis assays Cell reports High 34686350
2021 AIM2 regulates ZBP1 as part of a large multi-protein PANoptosome complex including AIM2, pyrin, ZBP1, ASC, caspase-1, caspase-8, RIPK3, RIPK1, and FADD; this complex drives inflammatory cell death (PANoptosis). AIM2 is required for ZBP1 integration into the complex during HSV-1 and F. novicida infection. Co-immunoprecipitation of multi-protein complex, AIM2/ZBP1/pyrin KO genetics, infectious disease mouse models, cell death assays Nature High 34471287
2022 ADAR1 prevents accumulation of endogenous Z-RNAs (from Alu inverted repeat dsRNAs); loss of ADAR1's Zα domain causes ZBP1 activation leading to caspase-8-dependent apoptosis and MLKL-mediated necroptosis. ZBP1 ablation fully rescues overt pathology caused by ADAR1 Zα-domain mutation, positioning ADAR1 as a negative regulator of sterile ZBP1 activation. Adar−/− and Adar1mZα/− mouse genetics combined with Zbp1−/− rescue, cell death assays, RNA-seq for Alu elements Nature High 35859175 35859176 35859177
2022 ADAR1 depletion or mutation results in Z-RNA accumulation and ZBP1 activation culminating in RIPK3-mediated necroptosis. The small molecule CBL0137 activates ZBP1 by triggering Z-DNA formation in cells, inducing ZBP1-dependent necroptosis in cancer-associated fibroblasts. ADAR1 KO/mutation in cancer cell lines, Z-RNA detection, ZBP1 KO controls, small molecule (CBL0137) treatment, tumor models Nature High 35614224
2021 Vaccinia virus protein E3 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 RIPK3-MLKL-dependent necroptosis. Substitution of Zα domains from ZBP1 or ADAR1 into E3 restores necroptosis suppression. E3 Zα mutant VACV, Z-RNA detection, ZBP1/RIPK3/MLKL KO cell lines, domain swap experiments Cell host & microbe High 34192517
2021 ZBP1 constitutive binding to RIPK1 is essential for TRIFosome (FADD-RIPK1-caspase-8 complex) formation, caspase-8-mediated cell death, and inflammasome activation in response to LPS and Yersinia pseudotuberculosis, positioning ZBP1 as an effector of the TRIF-dependent cell death pathway. ZBP1 KO cells/mice, co-immunoprecipitation of ZBP1-RIPK1, LPS and Yersinia infection models, caspase-8 and inflammasome activity assays Nature communications Medium 33397971
2022 ZBP1 promotes TLR3/TLR4-mediated inflammatory responses by facilitating timely delivery of RIPK1 to TRIF and enabling M1-ubiquitination of RIPK1, sustaining downstream inflammatory signaling cascades; Zbp1−/− mice show resistance to LPS-induced septic shock. Zbp1−/− mouse LPS sepsis model, co-immunoprecipitation of ZBP1-RIPK1-TRIF complex, RIPK1 ubiquitination assays Proceedings of the National Academy of Sciences of the United States of America Medium 35666872
2022 In human cells, ZBP1 associates with RIPK1, RIPK3, and ubiquitin ligases cIAP1 and LUBAC; ZBP1 promotes K63- and M1-linked ubiquitination of RIPK1 and ZBP1 itself via RIPK1 and RIPK3 as scaffolds (independently of their kinase activity) to activate TAK1- and IKK-mediated inflammatory signaling and cytokine production. Co-immunoprecipitation of ZBP1-RIPK1-RIPK3-cIAP1-LUBAC, ubiquitin chain-specific pulldowns, kinase-dead RIPK1/RIPK3 mutants, cytokine production assays in HT29 cells EMBO reports Medium 36268590
2022 Caspase-8 and FADD suppress spontaneous ZBP1 expression and thereby prevent spontaneous RIPK3-MLKL activation and necroptosis; in Caspase-8-deficient cells, increased ZBP1 expression is maintained by a positive feedback loop requiring cGAS-STING-TBK1 signaling. ZBP1 deletion suppresses spontaneous MLKL phosphorylation in Casp8−/− mice in vivo. Casp8−/− and FADD−/− mouse genetics, Zbp1−/− rescue, FLAG-MLKL knock-in reporter model, cGAS/STING/TBK1 inhibition, ZBP1 reconstitution Proceedings of the National Academy of Sciences of the United States of America High 36191211
2023 ZBP1 stabilizes Z-form mitochondrial DNA (mtDNA) and nucleates a cytosolic complex containing cGAS, RIPK1, and RIPK3 on destabilized mitochondrial genomes to sustain STAT1 phosphorylation and type I IFN signaling. ZBP1-deficient mice are protected from doxorubicin-induced cardiotoxicity. ZBP1 KO mice, Z-DNA detection in cardiomyocytes, co-immunoprecipitation of ZBP1-cGAS-RIPK1-RIPK3 complex, STAT1 phosphorylation assays, doxorubicin cardiotoxicity model Cell High 37352855
2023 A crisis-associated isoform of ZBP1 is induced by cGAS-STING signaling and binds telomeric-repeat-containing RNA (TERRA) transcripts from dysfunctional telomeres; TERRA-bound ZBP1 oligomerizes into filaments on the outer mitochondrial membrane and activates the MAVS innate immune adapter to trigger a lethal interferon response, driving replicative crisis. ZBP1 isoform characterization, TERRA-ZBP1 binding assays, mitochondrial membrane localization by imaging, MAVS co-immunoprecipitation, ZBP1 oligomerization assays, cGAS/STING inhibition Nature High 36755096
2024 ZBP1 causes skin inflammation by inducing both RIPK3-mediated necroptosis and RIPK1-caspase-8-mediated apoptosis in keratinocytes; ZBP1-induced caspase-8-mediated inflammation requires RHIM-dependent but kinase-activity-independent RIPK1 signaling. Complete prevention of skin inflammation requires combined deficiency in MLKL and caspase-8, and no cell-death-independent inflammatory signaling by ZBP1 was detected. Transgenic constitutively active ZBP1 (ZBP1ca) mouse epidermis model, MLKL/caspase-8 double KO, RIPK1 kinase-dead knock-in, histopathology, cytokine measurement Cell death and differentiation High 38849574
2024 STING upregulates both ZBP1 and MLKL transcriptionally; combined caspase-8 deficiency and STING-driven Z-nucleic acid accumulation activates ZBP1 and triggers formation of a ZBP1-RIPK1-RIPK3 complex independently of the FADD-RIPK1-RIPK3 complex, enabling necroptosis execution. STING and ZBP1 act as overlapping drivers of lethal dermatitis. Casp8E-KO mouse model, genetic deletion of STING/ZBP1/RIPK3, biochemical Co-IP of ZBP1-RIPK1-RIPK3 complex, SAVI preclinical mouse model rescue by Ripk3 co-deletion Nature High 40834903
2024 RIPK1's death domain (DD) is required to restrain ZBP1-mediated necroptosis; mutation R588E in the RIPK1 DD allows ZBP1 to activate RIPK3 independently of RIPK1 kinase activity, revealing that DD-dependent oligomerization and FADD interaction determine the mechanism of RIPK3 activation by ZBP1. Ripk1R588E/R588E knock-in mouse genetics, biochemical mechanistic studies, RIPK3 activation assays, comparison to RHIM mutant backgrounds Immunity Medium 38744293
2024 ZBP1 condensate formation via its Zαβ domain facilitates Z-nucleic acid binding and antiviral signal transduction; ZBP1 Zαβ dimerizes in a concentration-dependent manner, forms liquid-liquid phase-separated droplets upon Z-DNA/Z-RNA binding, and full-length ZBP1 forms amyloid-like puncta. RHIM domains form amyloid fibrils that cross-polymerize with RIPK1 depending on the 206IQIG209 core motif; RHIM-mutated ZBP1 impedes necroptosis. DLS, SAXS, in vitro condensate assays, in-cell imaging of amyloid-like puncta, RHIM domain mutagenesis, necroptosis assays in HT-29 cells, HSV/IAV infection models Cell death & disease Medium 38982083
2025 Host cell-encoded Z-RNAs (not viral Z-RNAs) are major and sufficient ZBP1-activating ligands during HSV-1 and IAV infection; these Z-RNAs map to intergenic endogenous retroelements embedded in abnormally long 3' extensions of host mRNAs generated by virus-driven disruption of transcription termination (DoTT) via inhibition of CPSF. Mutant viruses lacking ICP27 or NS1 (the CPSF inhibitors) fail to induce host Z-RNA accrual and show attenuated ZBP1 activation. Z-RNA mapping by sequencing in HSV/IAV-infected cells, ICP27/NS1 viral mutants, ectopic expression of ICP27/NS1, pharmacological CPSF blockade, ZBP1 KO controls Nature High 41082924
2024 A shorter alternatively-spliced ZBP1 isoform (ZBP1-S) containing Zα domains but lacking RHIMs acts as an endogenous inhibitor of full-length ZBP1-L by competing for Z-nucleic acid ligand binding, thereby suppressing ZBP1-L-mediated cell death and inflammation. Loss of ZBP1-S accelerates skin inflammation induced by ZBP1-mediated necroptosis. ZBP1-S-only knock-in mouse model, ZBP1-S KO mouse, cell death assays comparing ZBP1-S/ZBP1-L combinations, skin inflammation model The EMBO journal High 39300211
2017 ZBP1 (as zipcode binding protein 1/IGF2BP1 for β-actin mRNA): the KH3-KH4 di-domain of ZBP1 mediates β-actin mRNA recognition; KH4 recognizes a non-canonical GGA sequence via an enlarged dynamic hydrophobic groove, KH3 binds a core CA sequence with low specificity. Data-informed kinetic simulation reveals the overall binding reaction is driven by the second (KH4) binding event; ZBP1 concentration modulates the interaction. High-resolution NMR structures of KH3-KH4 with target RNA, kinetic binding simulation, affinity measurements Cell reports High 28147274
2007 ZBP1 (as zipcode binding protein 1) expression in metastatic tumor cells restores β-actin mRNA localization to lamellipodia, increases cell polarity, and reduces chemotaxis and tumor cell motility/invasion in vivo, establishing ZBP1 as a regulator of actin mRNA-dependent cell polarity. ZBP1 overexpression in MTLn3 cells, mRNA localization imaging, chemotaxis assays, multiphoton in vivo tumor imaging Journal of cell science Medium 17878234
2023 ZBP1 senses mitochondrial Z-form DNA and interacts with RIPK1 to activate RIPK1 kinase activity, inducing transcription of pro-inflammatory molecules via NF-κB in AD microglia; deletion of Zbp1 or inhibition of RIPK1 attenuates neuroinflammation and Aβ pathology in an AD mouse model. Amyloid-β-induced oxidative stress fragments and releases mtDNA into the cytoplasm where it forms Z-DNA. ZBP1 KO AD mouse model, RIPK1 inhibitor, Co-IP of ZBP1-RIPK1, Z-DNA detection in microglia, Aβ pathology and behavioral assays Immunity Medium 40902587
2013 DAI/ZBP1 suppresses HSV-1 replication in a DNA-sensing-independent manner requiring the Zβ and D3 domains (but not Zα). DAI colocalizes with the viral E3 ubiquitin ligase ICP0 in nuclear and cytoplasmic foci and co-immunoprecipitates with ICP0; DAI's anti-HSV-1 effect is not observed with ICP0-deleted mutant virus. DAI knockdown and overexpression in HepG2 cells, domain deletion mutants, co-immunoprecipitation of DAI-ICP0, viral replication assays Journal of virology Medium 23283962
2024 ZBP1 is amplified by palmitic acid-activated JNK pathway in steatotic livers; upon I/R injury, excessive ROS trigger ZBP1 activation by inducing its aggregation independently of Z-nucleic acid sensing, leading to RIPK1 kinase activation and downstream apoptosis and inflammation. ZBP1 KO mouse steatotic liver I/R model, JNK inhibition, RIPK1 kinase inhibitor, ZBP1 aggregation assays, ROS measurement The Journal of clinical investigation Medium 38743492
2023 TRIM32 is an E3 ubiquitin ligase that targets ZBP1 for proteasomal degradation; the cold-inducible RNA-binding protein CIRP competes with TRIM32 for ZBP1 binding (stabilizing ZBP1) when internalized into pulmonary endothelial cells via TLR4-mediated endocytosis during sepsis, thereby enhancing ZBP1-RIPK3-dependent PANoptosis. IP/MS identification of TRIM32, co-immunoprecipitation of CIRP-ZBP1 and TRIM32-ZBP1, ZBP1 ubiquitination/degradation assays, Zbp1−/− mouse sepsis model Military Medical Research Medium 39465383
2008 Human ZBP1 (hZBP1) overexpression does not affect IFN-β or IL-8 production induced by intracellular bacteria or cytosolic poly(dA-dT) in human A549 cells, and multiple hZBP1 siRNAs do not suppress IFN-β responses in human cells, indicating that human ZBP1 is not required for cytosolic DNA-induced IFN-β responses in human cells (NEGATIVE FINDING for the sensor function in human cells). hZBP1 siRNA knockdown in human cells, hZBP1 overexpression, IFN-β reporter and ELISA assays, comparison with mouse L929 cells Cellular microbiology Medium 18771559

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response. Nature 1397 17618271
2016 ZBP1/DAI is an innate sensor of influenza virus triggering the NLRP3 inflammasome and programmed cell death pathways. Science immunology 706 27917412
2021 AIM2 forms a complex with pyrin and ZBP1 to drive PANoptosis and host defence. Nature 635 34471287
2012 DAI/ZBP1/DLM-1 complexes with RIP3 to mediate virus-induced programmed necrosis that is targeted by murine cytomegalovirus vIRA. Cell host & microbe 631 22423968
2019 ZBP1 and TAK1: Master Regulators of NLRP3 Inflammasome/Pyroptosis, Apoptosis, and Necroptosis (PAN-optosis). Frontiers in cellular and infection microbiology 621 31850239
2020 The regulation of the ZBP1-NLRP3 inflammasome and its implications in pyroptosis, apoptosis, and necroptosis (PANoptosis). Immunological reviews 476 32729116
2020 Influenza Virus Z-RNAs Induce ZBP1-Mediated Necroptosis. Cell 473 32200799
1992 Interactions between double-stranded RNA regulators and the protein kinase DAI. Molecular and cellular biology 412 1357546
2020 Z-nucleic-acid sensing triggers ZBP1-dependent necroptosis and inflammation. Nature 402 32296175
2021 ADAR1 restricts ZBP1-mediated immune response and PANoptosis to promote tumorigenesis. Cell reports 366 34686350
2016 RIPK1 counteracts ZBP1-mediated necroptosis to inhibit inflammation. Nature 366 27819681
2016 DAI Senses Influenza A Virus Genomic RNA and Activates RIPK3-Dependent Cell Death. Cell host & microbe 354 27746097
2016 RIPK1 inhibits ZBP1-driven necroptosis during development. Nature 345 27819682
2022 ADAR1 masks the cancer immunotherapeutic promise of ZBP1-driven necroptosis. Nature 337 35614224
2009 DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB. EMBO reports 301 19590578
2022 ZBP1-dependent inflammatory cell death, PANoptosis, and cytokine storm disrupt IFN therapeutic efficacy during coronavirus infection. Science immunology 290 35587515
2001 Structure of the DLM-1-Z-DNA complex reveals a conserved family of Z-DNA-binding proteins. Nature structural biology 265 11524677
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
2019 The Nucleotide Sensor ZBP1 and Kinase RIPK3 Induce the Enzyme IRG1 to Promote an Antiviral Metabolic State in Neurons. Immunity 261 30635240
2017 ZBP1: Innate Sensor Regulating Cell Death and Inflammation. Trends in immunology 242 29236673
2023 Cooperative sensing of mitochondrial DNA by ZBP1 and cGAS promotes cardiotoxicity. Cell 211 37352855
2022 ADAR1 prevents autoinflammation by suppressing spontaneous ZBP1 activation. Nature 211 35859175
2017 Sensing of viral and endogenous RNA by ZBP1/DAI induces necroptosis. The EMBO journal 210 28716805
2020 ZBP1 promotes fungi-induced inflammasome activation and pyroptosis, apoptosis, and necroptosis (PANoptosis). The Journal of biological chemistry 193 33109609
2022 ADAR1 mutation causes ZBP1-dependent immunopathology. Nature 177 35859177
2022 ADAR1 averts fatal type I interferon induction by ZBP1. Nature 176 35859176
2017 ZBP1/DAI ubiquitination and sensing of influenza vRNPs activate programmed cell death. The Journal of experimental medicine 169 28634194
2021 ZBP1-MLKL necroptotic signaling potentiates radiation-induced antitumor immunity via intratumoral STING pathway activation. Science advances 160 34613770
2019 ZBP1 mediates interferon-induced necroptosis. Cellular & molecular immunology 153 31076724
2021 ZBP1 not RIPK1 mediates tumor necroptosis in breast cancer. Nature communications 149 33976222
2023 Telomere-to-mitochondria signalling by ZBP1 mediates replicative crisis. Nature 139 36755096
1999 Cloning of DLM-1, a novel gene that is up-regulated in activated macrophages, using RNA differential display. Gene 132 10564822
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
2023 PANoptosome signaling and therapeutic implications in infection: central role for ZBP1 to activate the inflammasome and PANoptosis. Current opinion in immunology 103 37267644
2023 Immune regulator IRF1 contributes to ZBP1-, AIM2-, RIPK1-, and NLRP12-PANoptosome activation and inflammatory cell death (PANoptosis). The Journal of biological chemistry 91 37557956
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 ZBP1 Protects Against mtDNA-Induced Myocardial Inflammation in Failing Hearts. Circulation research 89 36974722
2023 SARS-CoV-2 Z-RNA activates the ZBP1-RIPK3 pathway to promote virus-induced inflammatory responses. Cell research 88 36650286
2021 ZBP1 promotes LPS-induced cell death and IL-1β release via RHIM-mediated interactions with RIPK1. Nature communications 86 33397971
2023 ADAR1 and ZBP1 in innate immunity, cell death, and disease. Trends in immunology 84 36710220
2022 ZBP1: A Powerful Innate Immune Sensor and Double-Edged Sword in Host Immunity. International journal of molecular sciences 82 36142136
2017 Murine cytomegalovirus IE3-dependent transcription is required for DAI/ZBP1-mediated necroptosis. EMBO reports 82 28607035
2022 Human ZBP1 induces cell death-independent inflammatory signaling via RIPK3 and RIPK1. EMBO reports 74 36268590
2021 Viral Z-RNA triggers ZBP1-dependent cell death. Current opinion in virology 72 34688984
2008 IFNbeta responses induced by intracellular bacteria or cytosolic DNA in different human cells do not require ZBP1 (DLM-1/DAI). Cellular microbiology 69 18771559
2024 Fn-OMV potentiates ZBP1-mediated PANoptosis triggered by oncolytic HSV-1 to fuel antitumor immunity. Nature communications 68 38693119
2022 ZBP1 promotes inflammatory responses downstream of TLR3/TLR4 via timely delivery of RIPK1 to TRIF. Proceedings of the National Academy of Sciences of the United States of America 67 35666872
2024 Baicalin inhibits PANoptosis by blocking mitochondrial Z-DNA formation and ZBP1-PANoptosome assembly in macrophages. Acta pharmacologica Sinica 66 39223367
2023 The Z-nucleic acid sensor ZBP1 in health and disease. The Journal of experimental medicine 66 37450010
2024 Mechanism of lactic acidemia-promoted pulmonary endothelial cells death in sepsis: role for CIRP-ZBP1-PANoptosis pathway. Military Medical Research 65 39465383
2022 Caspase-8 and FADD prevent spontaneous ZBP1 expression and necroptosis. Proceedings of the National Academy of Sciences of the United States of America 63 36191211
2023 BPDE exposure promotes trophoblast cell pyroptosis and induces miscarriage by up-regulating lnc-HZ14/ZBP1/NLRP3 axis. Journal of hazardous materials 61 37167865
2002 Complex regulation of the human gene for the Z-DNA binding protein DLM-1. Nucleic acids research 60 11842111
2013 DNA sensing-independent inhibition of herpes simplex virus 1 replication by DAI/ZBP1. Journal of virology 57 23283962
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.) 56 37725754
2024 Sensing of mitochondrial DNA by ZBP1 promotes RIPK3-mediated necroptosis and ferroptosis in response to diquat poisoning. Cell death and differentiation 54 38493248
2024 ZBP1 causes inflammation by inducing RIPK3-mediated necroptosis and RIPK1 kinase activity-independent apoptosis. Cell death and differentiation 52 38849574
2022 ZBP1-Mediated Necroptosis: Mechanisms and Therapeutic Implications. Molecules (Basel, Switzerland) 50 36615244
2010 DAI (DLM-1/ZBP1) as a genetic adjuvant for DNA vaccines that promotes effective antitumor CTL immunity. Molecular therapy : the journal of the American Society of Gene Therapy 50 21157438
2023 Recent advances in ZBP1-derived PANoptosis against viral infections. Frontiers in immunology 49 37261341
2017 Mechanism of β-actin mRNA Recognition by ZBP1. Cell reports 49 28147274
2023 Triggering endogenous Z-RNA sensing for anti-tumor therapy through ZBP1-dependent necroptosis. Cell reports 47 37922310
2023 ZBP1 Drives IAV-Induced NLRP3 Inflammasome Activation and Lytic Cell Death, PANoptosis, Independent of the Necroptosis Executioner MLKL. Viruses 45 38005819
2024 The RIPK1 death domain restrains ZBP1- and TRIF-mediated cell death and inflammation. Immunity 42 38744293
2007 ZBP1 enhances cell polarity and reduces chemotaxis. Journal of cell science 42 17878234
2022 Emerging Role of ZBP1 in Z-RNA Sensing, Influenza Virus-Induced Cell Death, and Pulmonary Inflammation. mBio 41 35587190
2024 ZBP1-mediated apoptosis and inflammation exacerbate steatotic liver ischemia/reperfusion injury. The Journal of clinical investigation 39 38743492
2022 The innate sensor ZBP1-IRF3 axis regulates cell proliferation in multiple myeloma. Haematologica 37 33596642
2021 Endogenous tRNA-derived small RNA (tRF3-Thr-AGT) inhibits ZBP1/NLRP3 pathway-mediated cell pyroptosis to attenuate acute pancreatitis (AP). Journal of cellular and molecular medicine 35 34643045
2025 Epidermal ZBP1 stabilizes mitochondrial Z-DNA to drive UV-induced IFN signaling in autoimmune photosensitivity. Science immunology 34 40053607
2024 TRIM56 Modulates YBX1 Degradation to Ameliorate ZBP1-Mediated Neuronal PANoptosis in Spinal Cord Injury. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 34 39291396
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
2023 Necroptosis of macrophage is a key pathological feature in biliary atresia via GDCA/S1PR2/ZBP1/p-MLKL axis. Cell death & disease 32 36859525
2023 ZBP1 mediates the progression of Alzheimer's disease via pyroptosis by regulating IRF3. Molecular and cellular biochemistry 32 36964897
2022 Fisetin-induced cell death in human ovarian cancer cell lines via zbp1-mediated necroptosis. Journal of ovarian research 32 35538559
2024 ZBP1 and TRIF trigger lethal necroptosis in mice lacking caspase-8 and TNFR1. Cell death and differentiation 30 38548850
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 27 39465258
2023 Z-form nucleic acid-binding protein 1 (ZBP1) as a sensor of viral and cellular Z-RNAs: walking the razor's edge. Current opinion in immunology 27 37276820
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 26 40627395
2025 Targeted Degradation of ZBP1 with Covalent PROTACs for Anti-Inflammatory Treatment of Infections. Angewandte Chemie (International ed. in English) 22 40013409
2025 STING induces ZBP1-mediated necroptosis independently of TNFR1 and FADD. Nature 22 40834903
2025 Innate immune sensing of Z-nucleic acids by ZBP1-RIPK1 axis drives neuroinflammation in Alzheimer's disease. Immunity 21 40902587
2020 Zipcode Binding Protein 1 (ZBP1; IGF2BP1): A Model for Sequence-Specific RNA Regulation. Cold Spring Harbor symposia on quantitative biology 21 32086331
2024 ZBP1 promotes hepatocyte pyroptosis in acute liver injury by regulating the PGAM5/ROS pathway. Annals of hepatology 20 38331384
2024 IRF1 regulation of ZBP1 links mitochondrial DNA and chondrocyte damage in osteoarthritis. Cell communication and signaling : CCS 20 39026271
2023 PTRF-IL33-ZBP1 signaling mediating macrophage necroptosis contributes to HDM-induced airway inflammation. Cell death & disease 20 37454215
2022 Necrostatin-1 attenuates Caspase-1-dependent pyroptosis induced by the RIPK1/ZBP1 pathway in ventilator-induced lung injury. Cytokine 20 35780712
2025 Z-Nucleic Acid Sensing and Activation of ZBP1 in Cellular Physiology and Disease Pathogenesis. Immunological reviews 19 39748135
2024 Apoptosis dysfunction: unravelling the interplay between ZBP1 activation and viral invasion in innate immune responses. Cell communication and signaling : CCS 19 38402193
2024 ZBP1 condensate formation synergizes Z-NAs recognition and signal transduction. Cell death & disease 19 38982083
2023 ZBP1/DAI-Dependent Cell Death Pathways in Influenza A Virus Immunity and Pathogenesis. Current topics in microbiology and immunology 19 31970498
2024 Decoding the multiple functions of ZBP1 in the mechanism of sepsis-induced acute lung injury. Communications biology 18 39433574
2025 Host cell Z-RNAs activate ZBP1 during virus infections. Nature 17 41082924
2024 Quercetin Protects against Silicon dioxide Particles-induced spleen ZBP1-Mediated PANoptosis by regulating the Nrf2/Drp1/mtDNA axis. International immunopharmacology 17 39488923
2024 A shorter splicing isoform antagonizes ZBP1 to modulate cell death and inflammatory responses. The EMBO journal 16 39300211
2024 Z-nucleic acid sensor ZBP1 in sterile inflammation. Clinical immunology (Orlando, Fla.) 15 38346464
2024 Lipolysis engages CD36 to promote ZBP1-mediated necroptosis-impairing lung regeneration in COPD. Cell reports. Medicine 15 39255796
2025 ZBP1 senses Brucella abortus DNA triggering type I interferon signaling pathway and unfolded protein response activation. Frontiers in immunology 14 39850894

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