Affinage

Showing DHX58 — LGP2 is a alias.

DHX58

ATP-dependent RNA helicase DHX58 · UniProt Q96C10

Length
678 aa
Mass
76.6 kDa
Annotated
2026-06-09
100 papers in source corpus 43 papers cited in narrative 43 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

DHX58 (LGP2) is a DEXH-box RNA helicase that acts as a central, bidirectional rheostat of the RIG-I-like receptor (RLR) innate antiviral pathway, distinguished from RIG-I and MDA5 by the absence of N-terminal CARD signaling domains (PMID:16116171, PMID:16210631). It negatively regulates RIG-I-dependent signaling through several non-exclusive routes: a RIG-I-like repressor domain that ablates RIG-I self-association (PMID:17190814), formation of a complex with IPS-1/MAVS that competes with the kinase IKKε (PMID:17020950), prevention of TRIM25-mediated K63-ubiquitination of the RIG-I CARDs (PMID:31237466), and direct sequestration of the K63-ubiquitin-conjugating enzyme Ubc13/UBE2N via its Hel2i subdomain — a unifying mechanism that inactivates multiple K63 E3 ligases including TRAF6, TRIM25 and RNF125 (PMID:34965427). Critically, much of this negative regulation is independent of RNA binding and ATP hydrolysis (PMID:19278996, PMID:19211564). Conversely, LGP2 is a positive co-activator of MDA5 signaling: its ATPase activity allows it to engage diverse RNA substrates and synergize with MDA5 to potentiate IFN-β induction (PMID:20080593, PMID:23184951), and this requires direct LGP2–MDA5 association and dsRNA binding (PMID:23671710, PMID:27203181). Mechanistically, LGP2 binds dsRNA ends, translocates internally via ATP-driven 3'-strand tracking (PMID:38015453), and nucleates the assembly of more numerous but shorter MDA5 hetero-oligomeric filaments that are equally or more signaling-competent, driving CARD exposure, CARD–CARD cross-bridging into microclusters and downstream MAVS aggregation (PMID:25127512, PMID:33137199, PMID:41558484). This MDA5-facilitating function operates against authentic viral RNAs and endogenous unedited self-RNA in ADAR1-deficient cells (PMID:24550253, PMID:35156720). LGP2 activity is further tuned by direct interaction with the dsRNA-binding protein PACT through its CTD (PMID:31575732) and by Riplet-mediated delayed K63-ubiquitination (PMID:36515138). Beyond the RLR axis, LGP2 associates with Dicer and TRBP to inhibit dsRNA processing and miRNA maturation, thereby antagonizing antiviral RNAi (PMID:29351913, PMID:31799626), and it directly inhibits flavivirus NS5 RNA polymerase pre-elongation activity through its regulatory domain (PMID:37656756). LGP2 is itself an inducible gene, driven directly by IRF3 in part independently of cytokine signaling (PMID:41171864), and it influences CD8+ T cell survival and radiation-induced antitumor immunity (PMID:22841161, PMID:33087322).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 2005 High

    Established LGP2 as a distinct RLR member lacking CARD domains and as a negative regulator that interferes with viral RNA recognition, framing the entire field's question of how a CARD-less helicase modulates antiviral signaling.

    Evidence Overexpression, dsRNA binding assays, and IFN/NF-κB reporter assays in cells

    PMID:16116171 PMID:16210631

    Open questions at the time
    • Did not resolve direct molecular partners mediating inhibition
    • Did not distinguish RNA-dependent from RNA-independent mechanisms
  2. 2006 Medium

    Defined two molecular routes of negative regulation — a trans-acting repressor domain that blocks RIG-I self-association, and a competition with IKKε for IPS-1/MAVS — moving beyond phenomenology to specific protein interactions.

    Evidence Deletion mutagenesis, co-immunoprecipitation, and reporter assays in cells lacking RIG-I/MDA5

    PMID:17020950 PMID:17190814

    Open questions at the time
    • IPS-1 competition shown by single primary method in one lab
    • Quantitative contribution of each route to inhibition unresolved
  3. 2007 High

    Genetic knockout revealed LGP2's regulatory role is pathway-dependent — restraining RIG-I-mediated but enhancing MDA5-mediated responses — overturning a purely negative-regulator model.

    Evidence Lgp2 knockout mice challenged with poly(I:C), EMCV (MDA5) and VSV (RIG-I)

    PMID:17475874

    Open questions at the time
    • Mechanism distinguishing the opposing effects on RIG-I vs MDA5 not defined
    • Did not establish whether enzymatic activity underlies the positive role
  4. 2009 High

    Structural studies of the CTD/regulatory domain showed LGP2 caps dsRNA termini in a 5'-triphosphate-independent manner with 2:1 stoichiometry, and mutagenesis showed RNA binding and ATPase activity are dispensable for RIG-I inhibition — separating RNA sensing from interference.

    Evidence NMR and X-ray crystallography with RNA binding assays and helicase-motif mutagenesis

    PMID:19208642 PMID:19211564 PMID:19278996 PMID:19380577

    Open questions at the time
    • Did not explain how the same domain participates in MDA5 activation
    • Functional RNA ligands in cells not yet identified
  5. 2009 Medium

    Identified paramyxovirus V proteins as binding the LGP2 helicase C domain and disrupting its ATPase, providing a viral-evasion handle that pointed to ATPase function as biologically important.

    Evidence Co-IP, domain mapping, and ATPase assays for multiple V proteins

    PMID:19403670

    Open questions at the time
    • Consequence for endogenous LGP2 function in infection not yet shown
    • Single primary interaction method
  6. 2010 High

    Knock-in mice separating ATPase activity from expression demonstrated that LGP2 ATPase is required for its positive role upstream of both RIG-I and MDA5, establishing enzymatic activity as the basis of co-activation.

    Evidence Lgp2 knockout and Lgp2-K30A ATPase-dead knock-in mice with viral challenge and CARD-overexpression epistasis

    PMID:20080593

    Open questions at the time
    • Molecular substrate/target of ATPase-driven activity unresolved
    • Did not visualize the activated complex
  7. 2012 High

    Defined the positive function as MDA5-specific co-operation requiring dsRNA binding, helicase domain IV, and physical LGP2–MDA5 interaction, while confirming RIG-I-directed inhibition — clarifying the dual model.

    Evidence Reporter assays, Co-IP, domain deletions, and siRNA knockdown; quantitative RNA binding, single-molecule FRET, and ATPase assays with EMCV infection

    PMID:23184951 PMID:23671710

    Open questions at the time
    • Structural basis of LGP2–MDA5 cooperation not yet defined
    • How ATPase diversifies RNA recognition mechanistically unclear
  8. 2012 Medium

    Extended LGP2 biology beyond cytosolic sensing by showing a CD8+ T cell-intrinsic prosurvival role and demonstrated V-protein-mediated cooperative RIG-I inhibition, broadening the protein's physiological reach.

    Evidence Adoptive transfer, Lgp2-deficient mice, death-receptor pathway analysis; Co-IP and reporter assays with PIV5 V protein

    PMID:22301134 PMID:22841161

    Open questions at the time
    • Mechanism linking LGP2 to CD95/death-receptor signaling not molecularly defined
    • Single-lab observations
  9. 2014 High

    Mechanistic and structural work showed LGP2 increases the rate of MDA5–RNA engagement and reprograms filament assembly into shorter, more numerous, signaling-competent filaments, and identified a specific stimulatory viral RNA (EMCV L-region antisense), converting the co-activation model into a defined biochemical mechanism.

    Evidence Electron microscopy, in vitro filament assembly, LGP2/RNA complex purification with RNA-seq, and EMCV reverse genetics

    PMID:24550253 PMID:24829334 PMID:25127512

    Open questions at the time
    • Did not resolve the conformational change LGP2 imparts on MDA5
    • How filament length translates to optimized signaling unclear
  10. 2014 Medium

    Connected LGP2 to therapeutic context by showing it suppresses IFN-β to confer tumor radioresistance, with IR inducing LGP2 in a negative feedback loop.

    Evidence siRNA ISG screen, LGP2 knockdown/overexpression, IFN-β neutralization, and IFN-receptor knockout MEFs

    PMID:24434553

    Open questions at the time
    • Which LGP2 regulatory arm (RIG-I-inhibitory vs MDA5-activating) dominates in this setting unresolved
    • Single-lab study
  11. 2016 High

    Co-crystal structures of LGP2–dsRNA in distinct nucleotide states defined LGP2 as a MDA5-helicase/RIG-I-CTD chimera that caps dsRNA ends with a 1-bp-longer footprint and require RNA binding for MDA5 enhancement, unifying the structural and functional models.

    Evidence X-ray crystallography in multiple states with RNA binding and MDA5 filament assembly assays

    PMID:27203181

    Open questions at the time
    • Dynamics of end-binding-to-internal-translocation transition not captured
    • Direct contacts with MDA5 within a filament not yet resolved
  12. 2017 Medium

    Demonstrated upstream positive regulation in physiologically relevant infection (HCV in hepatocytes) requiring ATPase activity, and identified PUM1 as an upstream repressor of LGP2 expression that gates an innate immunity gene cascade.

    Evidence LGP2 knockout hepatocytes, RNA-IP, ATPase-dead mutants; PUM1/LGP2 double-knockdown epistasis with qRT-PCR

    PMID:28090671 PMID:28760986

    Open questions at the time
    • Direct LGP2 substrate RNAs in HCV not defined
    • Single-lab observations
  13. 2018 High

    Broadened LGP2 function to RNAi suppression (Dicer association) and defined a unifying negative-regulatory principle — interference with TRAF ubiquitin ligases — independent of ATPase, RNA binding, or CTD.

    Evidence Co-IP, in vitro Dicer cleavage assays, LGP2 knockout cells; Co-IP and ubiquitin ligase activity assays with TRAF2/3/5/6

    PMID:29351913 PMID:29661858

    Open questions at the time
    • Whether Dicer and TRAF interactions occur via the same surface unresolved
    • TRAF interference shown in single lab
  14. 2018 Medium

    Mapped V-protein recognition residues (LGP2 R455, MDA5 R806) and identified an FMDV Lpro cleavage site (RGRAR) that inactivates LGP2's antiviral effect, defining precise molecular determinants of viral antagonism.

    Evidence Site-directed mutagenesis, Co-IP, IFN reporter assays; Lpro cleavage and mutagenesis with viral replication assays

    PMID:23269789 PMID:29958302

    Open questions at the time
    • Structural basis of V-protein/LGP2 recognition not resolved
    • Single-lab cleavage characterization
  15. 2019 High

    Identified PACT as a direct CTD partner whose interaction is required for BOTH the RIG-I-inhibitory and MDA5-activating arms, providing a single molecular node controlling LGP2's dual function.

    Evidence Co-IP, purified-protein pulldown, separation-of-function point mutation, mass spectrometry, and IFN reporter assays

    PMID:31575732

    Open questions at the time
    • How one PACT-binding surface enables opposite outcomes mechanistically unclear
    • In vivo requirement not tested
  16. 2019 Medium

    Resolved a molecular mechanism of RIG-I inhibition: LGP2 binds TRIM25 to block K63-ubiquitination of the RIG-I CARDs, independent of RNA binding, ATPase, and CTD.

    Evidence Mass spectrometry, Co-IP, K63-ubiquitination assays, and Dhx58-/- dendritic cells

    PMID:31237466

    Open questions at the time
    • Whether TRIM25 interference and Ubc13 sequestration are the same event unresolved at the time
    • Single-lab study
  17. 2020 High

    Provided structural mechanism of MDA5 activation — LGP2 incorporates into dsRNA-bound fibers as hetero-oligomers and induces conformational change exposing MDA5 CARDs — and linked LGP2 to MDA5-dependent antitumor IFN in dendritic cells, plus extended anti-RNAi function and a TRBP-miRNA/apoptosis axis.

    Evidence Single-molecule biophysics and limited proteolysis CARD-exposure assays; host LGP2 knockout tumor models; in vivo vsiRNA profiling; LGP2–TRBP Co-IP and miRNA profiling

    PMID:31799626 PMID:33087322 PMID:33137199 PMID:34343211

    Open questions at the time
    • Atomic-resolution view of the LGP2-MDA5 interface still lacking
    • How RNAi suppression and RLR activation are coordinated in the same cell unclear
  18. 2021 High

    Unified the negative-regulatory mechanism by showing LGP2 directly sequesters the K63-conjugating enzyme Ubc13/UBE2N via its Hel2i subdomain, thereby inactivating multiple E3 ligases (TRAF6, TRIM25, RNF125), and identified mRNA-level (m6A/DDX5-METTL3) control of DHX58.

    Evidence Co-IP, in vitro ubiquitination assays, Hel2i deletion mutants; m6A assays and RNA pulldown for DDX5/METTL3 regulation

    PMID:33909701 PMID:34965427

    Open questions at the time
    • Structural basis of Hel2i–Ubc13 interaction not resolved
    • How LGP2 prioritizes Ubc13 sequestration over MDA5 activation in vivo unclear
  19. 2022 High

    Defined LGP2 ubiquitination as a fine-tuning layer (Riplet-mediated, delayed K63 chains) and established LGP2's requirement for sensing endogenous unedited self-RNA in ADAR1-deficient cells and for MDA5-RNA complex stability during HDV infection, including a gain-of-function variant Q425R.

    Evidence MS ubiquitination mapping and K-to-R mutants; LGP2 knockout in ADAR1-deficient cells; LGP2 reconstitution and pulldowns in hepatocyte models

    PMID:35156720 PMID:36152765 PMID:36515138

    Open questions at the time
    • Functional consequence of Riplet-driven LGP2 ubiquitination only partially resolved
    • Several findings from single labs
  20. 2023 High

    Revealed a direct antiviral effector role beyond signaling regulation: the LGP2 regulatory domain binds flavivirus NS5 RdRP and inhibits its pre-elongation polymerase activity in an RNA-binding-independent manner.

    Evidence Co-IP, biolayer interferometry, in vitro RdRP assays, and RNA-binding-defective LGP2 mutants

    PMID:37656756

    Open questions at the time
    • In vivo contribution of NS5 inhibition to flavivirus control not established
    • Structure of the LGP2-RD/NS5 complex unresolved
  21. 2024 High

    Mechanistically detailed LGP2's end-binding, ATP-driven 3'-strand-tracking translocation and noncooperative internal dsRNA binding that nucleates shorter MDA5 filaments via a C-terminal tail contact, and confirmed Ubc13 sequestration as the unifying negative-regulatory mechanism.

    Evidence Single-molecule displacement and methylated-RNA assays, NTPase assays, EM filament assembly with molecular modeling; ubiquitination assays with Hel2i mutants

    PMID:34965427 PMID:38015453 PMID:38309507

    Open questions at the time
    • How methyl-RNA sensitivity is exploited to discriminate self vs nonself in vivo unclear
    • Quantitative coupling of translocation to filament nucleation incomplete
  22. 2024 Medium

    Identified HOIL1 as an E3 ligase promoting LGP2 ubiquitination that drives MDA5 oligomerization, MAVS aggregation and IFN induction, adding a positive ubiquitin-dependent regulatory layer.

    Evidence Co-IP, ubiquitination assays, MDA5 oligomerization and MAVS aggregate detection (preprint)

    PMID:38617308

    Open questions at the time
    • Preprint, not peer-reviewed
    • Ubiquitination site and chain type not fully defined
  23. 2026 High

    Cryo-EM with AFM provided an integrated structural mechanism from dsRNA end-binding and translocation through MDA5-LGP2 short-filament formation, CARD-CARD cross-bridging into microclusters, and MAVS filament stimulation — closing the loop from RNA recognition to signaling output.

    Evidence Cryo-EM, high-speed AFM, filament assembly and MAVS aggregate assays

    PMID:41558484

    Open questions at the time
    • Stoichiometry and kinetics of microcluster-to-MAVS transition incompletely defined
    • Regulation of this assembly by PACT/ubiquitination not integrated structurally
  24. 2025 Medium

    Showed LGP2 induction has a cytokine-independent component driven directly by IRF3 at the LGP2 promoter, clarifying how LGP2 levels are set during early infection.

    Evidence Genetic/chemical ablation of cytokine signaling, IRF3-5D overexpression, and LGP2 promoter reporter assays

    PMID:41171864

    Open questions at the time
    • Relative in vivo contribution of IRF3-driven vs cytokine-driven induction unresolved
    • Single-lab study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the bidirectional functions of LGP2 — RIG-I inhibition, MDA5 activation, RNAi suppression, and direct viral polymerase inhibition — are coordinated and prioritized within a single cell over the course of infection remains unresolved.
  • No integrated model of how RNA-binding/ATPase-dependent (MDA5 activation) versus RNA-independent (Ubc13/TRAF/TRIM25 interference) arms are switched
  • Spatiotemporal control of LGP2 partner choice unknown
  • Physiological role of LGP2-NS5 and LGP2-Dicer/TRBP axes relative to RLR regulation untested in vivo

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 6 GO:0098772 molecular function regulator activity 5 GO:0016787 hydrolase activity 4 GO:0140657 ATP-dependent activity 4 GO:0060089 molecular transducer activity 3
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 2 R-HSA-8953854 Metabolism of RNA 2
Partners
DICER1MAVSMDA5PACTRIG-ITRBPTRIM25UBE2N
Complex memberships
LGP2-MDA5-dsRNA filament hetero-oligomer

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 LGP2 lacks N-terminal CARD domains and functions as a negative regulator of antiviral signaling by interfering with viral RNA recognition by RIG-I and MDA5; LGP2 binds double-stranded RNA (dsRNA) but not single-stranded RNA, and overexpression inhibits Sendai virus and Newcastle disease virus signaling to IFN-stimulated regulatory element- and NF-κB-dependent pathways. Overexpression in cells, dsRNA binding assays, reporter gene assays (IFN-stimulated regulatory element and NF-κB reporters), quantitative PCR Journal of immunology High 16116171 16210631
2006 LGP2 contains a repressor domain (RD) analogous to that in RIG-I that interacts in trans with RIG-I to ablate its self-association and downstream signaling to IPS-1; LGP2 also binds HCV RNA via this domain. RNA binding studies, deletion mutant analysis, reporter assays (IFN-β promoter), co-immunoprecipitation, overexpression in cells lacking RIG-I/MDA5 Proceedings of the National Academy of Sciences of the United States of America High 17190814
2006 LGP2 inhibits antiviral signaling independently of dsRNA or virus by engaging in a protein complex with IPS-1 (MAVS), and competes with the kinase IKKi/IKKε for a common interaction site on IPS-1. Co-immunoprecipitation, reporter assays, overexpression in mammalian cells Journal of virology Medium 17020950
2007 Lgp2-deficient mice show enhanced type I IFN production in response to cytosolic poly(I:C), but loss of LGP2 impairs IFN production in response to encephalomyocarditis virus (an MDA5-dependent virus) while conferring resistance to VSV (a RIG-I-dependent virus), indicating a disparate regulatory role for LGP2 depending on the viral recognition pathway. Lgp2 knockout mouse generation, viral infection assays, poly(I:C) stimulation, IFN-β measurements Journal of immunology High 17475874
2009 NMR solution structures of LGP2 C-terminal domain (CTD) reveal a conserved fold with a large basic surface; the RNA binding loop in LGP2 CTD enables binding of both dsRNA and 5'-triphosphated ssRNA. Mutation of the basic surface and the RNA binding loop abrogates RNA binding. NMR structure determination, NMR chemical shift perturbation, site-directed mutagenesis, RNA binding assays The Journal of biological chemistry High 19380577
2009 Crystal structure of LGP2 regulatory domain (RD) at 2.6 Å reveals it binds dsRNA in a 5'-triphosphate-independent manner, distinct from RIG-I RD which senses 5'-triphosphate RNA; receptor-specific residues in the RNA binding site confer pattern selectivity. X-ray crystallography, in vitro RNA binding assays, in vivo signaling reporter assays, homology modeling Nucleic acids research High 19208642
2009 Crystal structure of human LGP2 CTD bound to 8-bp dsRNA at 2.0 Å resolution shows two LGP2 CTD molecules bind the termini of dsRNA in a 2:1 stoichiometry. LGP2 binds blunt-ended dsRNA and dsRNA with protruding termini weakly. Full-length LGP2 mutations abolishing dsRNA binding retain the ability to inhibit RIG-I signaling. X-ray crystallography, gel filtration chromatography, analytical ultracentrifugation, cell-based signaling assays The Journal of biological chemistry High 19278996
2009 Neither enzymatic (ATPase) activity nor RNA binding is required for LGP2 to negatively regulate antiviral signaling, supporting an RNA-independent interference mechanism. In contrast, MDA5 and RIG-I motif mutations that abolish ATP hydrolysis can produce constitutively active signaling proteins. Site-directed mutagenesis of conserved helicase motifs, ATPase assays, RNA binding assays, IFN reporter assays The Journal of biological chemistry High 19211564
2009 Paramyxovirus V proteins associate with LGP2 through the helicase C domain (a region highly homologous between MDA5 and LGP2 but not RIG-I), and this interaction disrupts ATP hydrolysis mediated by LGP2. Co-immunoprecipitation, ATPase activity assays, domain mapping with truncation mutants Journal of virology Medium 19403670
2010 LGP2-deficient mice (Lgp2-/-) show impaired RIG-I- and MDA5-mediated antiviral responses, and ATPase-deficient knock-in mice (Lgp2-K30A) show similarly impaired IFN-β production to diverse RNA viruses, demonstrating that LGP2 ATPase activity is required for its positive regulatory role acting upstream of RIG-I and MDA5. LGP2 and its ATPase activity are dispensable for responses to synthetic RNA ligands. Knockout and knock-in mouse generation, viral infection assays, IFN-β measurement, overexpression of RIG-I/MDA5 CARD domains in Lgp2-/- fibroblasts Proceedings of the National Academy of Sciences of the United States of America High 20080593
2012 LGP2 potentiates IFN induction specifically through co-operation with MDA5, not RIG-I, and this co-operation requires dsRNA binding by LGP2 and helicase domain IV, both of which are required for LGP2 to physically interact with MDA5. LGP2 acts as an inhibitor of RIG-I-dependent signaling. IFN reporter assays, co-immunoprecipitation, domain deletion mutants, siRNA knockdown PloS one Medium 23671710
2012 LGP2 ATPase activity enables the protein to associate with intrinsically poor RNA substrates (diversified RNA recognition), and this property is required for LGP2 to synergize with MDA5 to potentiate IFNβ transcription during EMCV infection. Basal ATP hydrolysis is distinct from dsRNA-stimulated hydrolysis. Quantitative dsRNA binding assays, ATPase activity assays, single-molecule FRET analysis, IFN reporter assays, viral infection assays The Journal of biological chemistry High 23184951
2012 Paramyxovirus PIV5 V protein interacts with LGP2, forms a complex with RIG-I in the presence of V protein, and cooperatively inhibits RIG-I ligand-induced IFN induction. Other paramyxovirus V proteins also bind LGP2 and demonstrate LGP2-dependent inhibition of RIG-I signaling. Co-immunoprecipitation, IFN reporter assays, siRNA knockdown of LGP2 Journal of virology Medium 22301134
2012 LGP2 is required in CD8+ T cells for survival and fitness during antigen-specific expansion; TCR signaling induces LGP2 expression, and LGP2 regulates death-receptor signaling to impart sensitivity to CD95-mediated cell death (prosurvival signal). Adoptive transfer experiments, Lgp2-deficient mice, biochemical studies of death-receptor signaling pathway, viral infection models (WNV, LCMV) Immunity Medium 22841161
2012 Single amino acid R806 in MDA5 is essential for recognition by diverse paramyxovirus V proteins; the analogous LGP2 R455 is required for recognition by measles V protein. Substitution of the analogous RIG-I residue L714 confers V protein recognition to RIG-I. Site-directed mutagenesis, IFN reporter assays, co-immunoprecipitation Journal of virology Medium 23269789
2014 LGP2 increases the initial rate of MDA5-RNA interaction, regulates MDA5 filament assembly to produce more numerous, shorter MDA5 filaments, and these shorter LGP2-regulated filaments generate equivalent or greater antiviral signaling activity than longer MDA5-only filaments. Electron microscopy, biochemical RNA binding assays, MDA5 filament assembly assays, in vivo signaling reporter assays Molecular cell High 25127512
2014 V protein interaction with LGP2 specifically prevents its coactivation of MDA5 signaling, but LGP2's negative regulatory capacity (inhibition of RIG-I and MDA5) is not affected by V protein interaction. V protein-insensitive LGP2/MDA5 mutants, IFN reporter assays, co-immunoprecipitation Journal of virology Medium 24829334
2014 LGP2/RNA complexes purified from EMCV-infected cells are enriched for RNA highly stimulatory for MDA5, specifically the L region of EMCV antisense RNA. Genomic deletion of the L region in EMCV generates viruses less potent at stimulating MDA5-dependent IFN production. LGP2/RNA complex purification from infected cells, RNA sequencing, in vitro transcription, reverse genetics (genomic deletion) eLife High 24550253
2014 LGP2 depletion in tumor cells increases cell death following ionizing radiation (IR) by enhancing IFNβ production; LGP2 suppresses IFNβ expression and thereby confers radioresistance. IR also induces LGP2 expression, creating a negative feedback loop. siRNA screen (89 ISGs), LGP2 knockdown/overexpression in cancer cell lines, cell viability assays, IFNβ neutralizing antibody experiments, IFN receptor knockout MEFs Proceedings of the National Academy of Sciences of the United States of America Medium 24434553
2016 Co-crystal structures of chicken LGP2 with dsRNA reveal fully or semi-closed conformations depending on presence of nucleotide. LGP2 caps blunt, 3' or 5' overhang dsRNA ends with a footprint 1 bp longer than RIG-I. RNA binding is required for LGP2-mediated enhancement of MDA5 activation. LGP2 resembles a chimera with MDA5-like helicase domain and RIG-I-like CTD. X-ray crystallography, dsRNA binding assays, functional IFN reporter assays, MDA5 filament assembly assays Molecular cell High 27203181
2017 LGP2 is a positive regulator of HCV infection-induced IFN signaling acting upstream of MDA5; upon HCV infection, LGP2 and MDA5 interact, and this interaction enhances MDA5/HCV RNA association. ATPase activity of LGP2 is critical for assisting MDA5/HCV RNA interaction. LGP2 knockout in hepatocytes, co-immunoprecipitation, RNA immunoprecipitation, ATPase-deficient LGP2 mutants, IFN production assays Hepatology Medium 28090671
2017 PUM1 is a negative regulator of LGP2 expression; knockdown of PUM1 upregulates LGP2, which then drives a cascade upregulation of innate immunity genes (CXCL10, IL6, PKR in phase 1; RIG-I, MDA5, IFNβ in phase 2). Simultaneous depletion of PUM1 and LGP2 abrogates this cascade. siRNA knockdown (PUM1 alone and in combination with LGP2), quantitative RT-PCR, IFNβ functional assays Proceedings of the National Academy of Sciences of the United States of America Medium 28760986
2018 LGP2 associates with Dicer and inhibits cleavage of dsRNA into siRNAs both in vitro and in cells, thereby antagonizing RNA interference. Genetic loss of LGP2 uncovers dsRNA-mediated RNAi. LGP2 is an IFN-stimulated gene that can suppress antiviral RNAi. Co-immunoprecipitation of LGP2-Dicer complex, in vitro Dicer cleavage assays with purified proteins, RNAi reporter assays in cells, LGP2 knockout cells The EMBO journal High 29351913
2018 LGP2 associates with TRAF2, TRAF3, TRAF5, and TRAF6 (via their C-termini) and interferes with TRAF ubiquitin ligase activity, negatively regulating antiviral signaling. This TRAF interference is independent of LGP2 ATP hydrolysis, RNA binding, or CTD. LGP2 can regulate TRAF-mediated signaling in trans, including IL-1β, TNFα, and cGAMP pathways. Co-immunoprecipitation, ubiquitin ligase activity assays, LGP2 domain mutants, reporter assays across multiple signaling pathways EMBO reports Medium 29661858
2018 FMDV Leader protease (Lpro) cleaves LGP2 at a conserved RGRAR sequence in a helicase motif. Lpro co-localizes and co-immunoprecipitates with LGP2 in the cytoplasm. Cleavage of LGP2 reverts its antiviral effect and reduces IFN-β production, representing a viral immune evasion mechanism. Co-expression/co-immunoprecipitation, site-directed mutagenesis (RGRAR→EGEAE), IFN-β mRNA measurement, viral replication assays PLoS pathogens Medium 29958302
2019 LGP2 directly interacts with the dsRNA-binding protein PACT via its C-terminal regulatory domain (CTD). The LGP2-PACT interaction is necessary for inhibiting RIG-I-dependent responses and for amplifying MDA5-dependent responses. A single point mutation in LGP2 disrupting PACT interaction abolishes both regulatory functions. Co-immunoprecipitation, pulldown with purified recombinant proteins, site-directed mutagenesis, IFN reporter assays, mass spectrometry Science signaling High 31575732
2019 LGP2 inhibits RIG-I signaling by interacting with the E3 ubiquitin ligase TRIM25 and preventing TRIM25-mediated K63-specific ubiquitination of the RIG-I N-terminus required for signaling activation. RNA binding, ATP hydrolysis, and CTD are dispensable for this inhibition. Mass spectrometry, co-immunoprecipitation, K63-ubiquitination assays, Dhx58-/- bone marrow-derived dendritic cells, reporter assays Journal of interferon & cytokine research Medium 31237466
2020 LGP2 facilitates MDA5 fiber assembly by being incorporated into dsRNA-bound fibers (average inter-molecular distance ~32 nm), forming hetero-oligomers with MDA5. LGP2 induces significant conformational changes on MDA5 (revealed by limited protease digestion), promoting exposure of its CARDs and converting MDA5 to an active conformation. MDA5 maintains its active conformation after fiber dissociation by ATP hydrolysis. Biochemical fiber assembly assays, single-molecule biophysical approaches, limited protease digestion, CARD exposure assays, IFN-β reporter assays Nucleic acids research High 33137199
2020 LGP2 is essential for optimal antitumor control by ionizing radiation via promotion of MDA5-mediated type I IFN signaling in dendritic cells; absence of LGP2 in DCs dampens type I IFN production and DC priming capacity. Host LGP2 knockout mouse models, tumor irradiation, DC function assays, IFN production measurement, poly I:C/MDA5 agonist experiments Cancer research Medium 33087322
2021 LGP2 inhibits K63-linked polyubiquitination by directly associating with and sequestering the K63-Ub-conjugating enzyme Ubc13/UBE2N. The LGP2 helicase subdomain Hel2i mediates this protein interaction, which inactivates multiple K63-Ub ligases including TRAF6, TRIM25, and RNF125. Co-immunoprecipitation, in vitro ubiquitination assays, domain mapping with Hel2i deletion mutants, NF-κB reporter assays Cell reports High 34965427
2021 DDX5 interacts with METTL3 to promote m6A modification of DHX58/LGP2 mRNA transcripts, which promotes DHX58 translation and activates the DHX58-TBK1 pathway, inhibiting antiviral innate response. Co-immunoprecipitation, m6A methylation assays, RNA pull-down, overexpression and knockdown in cells, in vivo viral infection models PLoS pathogens Medium 33909701
2022 LGP2 undergoes K63-linked polyubiquitination by the Riplet ubiquitin ligase in response to dsRNA or viral infection (with a delay relative to RIG-I ubiquitination). Ubiquitination-defective LGP2 mutations increase type I IFN at late phase but attenuate other antiviral proteins (SP100, PML, ANKRD1), demonstrating that Riplet-mediated LGP2 ubiquitination fine-tunes RIG-I-dependent antiviral responses. Mass spectrometry identification of ubiquitination sites, ubiquitination assays with Riplet, K-to-R mutants of LGP2, viral infection timing experiments EMBO reports Medium 36515138
2022 LGP2 is essential for the MDA5-dependent type I IFN response in ADAR1-deficient human cells sensing endogenous unedited self-RNAs; this requires LGP2's canonical RNA sensing and MDA5 facilitation functions. LGP2 expression is required for tumor cell sensitivity to ADAR1 loss. LGP2 knockout in ADAR1-deficient human cells, IFN reporter assays, functional rescue experiments The EMBO journal Medium 35156720
2022 LGP2 RNA binding is a prerequisite for formation of stable MDA5-RNA complexes during HDV infection; both RNA binding and ATPase activities of LGP2 are required for MDA5-mediated IFN response. A natural LGP2 variant Q425R enhances MDA5-RNA binding and accelerates IFN responses. LGP2 knockout in HepaRG-NTCP cells and primary hepatocytes, LGP2 reconstitution with variants, pull-down assays for LGP2-MDA5-RNA complexes, IFN quantification Journal of hepatology High 36152765
2023 LGP2 directly interacts with flavivirus NS5 RNA-dependent RNA polymerase; the LGP2 regulatory domain (RD) directly binds NS5 RdRP (confirmed by biolayer interferometry). LGP2 inhibits NS5 polymerase activities at pre-elongation but not elongation stages in vitro, independent of RNA binding by LGP2. Co-immunoprecipitation, confocal immunofluorescence, biolayer interferometry, in vitro RdRP assays, RNA-binding defective LGP2 mutants PLoS pathogens High 37656756
2024 LGP2 prefers binding blunt-ended dsRNA over internal dsRNA or RNA overhangs, associates with blunt-ends faster than overhangs, and is insensitive to 5'-triphosphate, Cap0, or Cap1 RNA modifications (unlike RIG-I). LGP2 uses ATPase activity to translocate along dsRNA via a 3'-strand tracking mechanism and can displace biotin-streptavidin interactions; this translocation is hindered by methylated RNA patches. Biochemical RNA binding assays, ATPase assays, single-molecule displacement assays, methylated RNA substrate experiments Nucleic acids research High 38015453
2024 LGP2 binds to dsRNA at internal sites through noncooperative ATP hydrolysis (unlike cooperative ATP hydrolysis by MDA5). LGP2 has low nucleic acid selectivity and can hydrolyze GTP and CTP in addition to ATP. Binding of LGP2 to internal dsRNA sites promotes nucleation of MDA5 filament assembly resulting in shorter filaments. The LGP2 C-terminal tail forms key contacts with MDA5 in an internally bound MDA5-LGP2-RNA complex. Electron microscopy, biochemical NTPase assays, filament assembly assays, molecular modeling The Journal of biological chemistry High 38309507
2024 LGP2 inhibition of K63-ubiquitination extends to Ubc13/UBE2N sequestration via the Hel2i helicase subdomain; this was established as the unifying mechanism for LGP2-mediated negative regulation (previously shown separately for TRAF proteins and TRIM25). Co-immunoprecipitation, in vitro ubiquitination assays with multiple E3 ligases (TRAF6, TRIM25, RNF125), Hel2i domain deletion mutants Cell reports High 34965427
2024 HOIL1 E3 ubiquitin ligase interacts with LGP2 and facilitates its ubiquitination. HOIL1-mediated LGP2 ubiquitination promotes MDA5 oligomerization, translocation to mitochondrial-associated membranes, MAVS aggregate formation, and downstream IFN induction. Co-immunoprecipitation, ubiquitination assays, MDA5 oligomerization assays, MAVS aggregate detection, IFN reporter assays bioRxivpreprint Medium 38617308
2020 LGP2 inhibits Dicer processing of dsRNA-vRIs into vsiRNAs in vivo during authentic viral infection (Nodamura virus, SINV, influenza), extending its anti-RNAi function beyond artificial dsRNA substrates. Small RNA sequencing of vsiRNAs in vivo, LGP2-expressing virus infection models, comparison with IFN-deficient conditions PLoS pathogens Medium 34343211
2020 LGP2 interacts with TRBP (TAR-RNA binding protein) and inhibits maturation of TRBP-bound miRNAs, leading to upregulation of apoptosis regulatory genes (caspases-2, -8, -3, -7) including through repression of miR-106b during viral infection. Co-immunoprecipitation of LGP2-TRBP, miRNA profiling, gene expression analysis, Sendai virus infection model Nucleic acids research Medium 31799626
2026 Cryo-EM structure reveals LGP2 initially binds dsRNA ends and translocates along RNA via ATP hydrolysis. LGP2 forms filament-like assemblies with MDA5 along internal dsRNA, promoting MDA5 filament nucleation. LGP2 and MDA5 form short RNA filaments that cross-bridge via CARD-CARD interactions into filament microclusters, which stimulate MAVS filament formation. Cryo-electron microscopy, high-speed atomic force microscopy, biochemical filament assembly assays, MAVS aggregate formation assays Molecular cell High 41558484
2025 LGP2 induction during viral infection has a cytokine-independent component: a fraction of LGP2 upregulation is driven directly by IRF3 (activated form IRF3-5D) and to a lesser extent NF-κB p65 acting at the LGP2 promoter, independent of IFN/cytokine paracrine/autocrine signaling. Genetic deletion/chemical inhibition of IFN/cytokine signaling, IRF3-5D overexpression, LGP2 promoter reporter assays, TLR3 and RLR pathway dissection The Journal of general virology Medium 41171864

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. Journal of immunology (Baltimore, Md. : 1950) 1311 16116171
2006 Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2. Proceedings of the National Academy of Sciences of the United States of America 586 17190814
2010 LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses. Proceedings of the National Academy of Sciences of the United States of America 522 20080593
2005 The RNA helicase Lgp2 inhibits TLR-independent sensing of viral replication by retinoic acid-inducible gene-I. Journal of immunology (Baltimore, Md. : 1950) 486 16210631
2007 Loss of DExD/H box RNA helicase LGP2 manifests disparate antiviral responses. Journal of immunology (Baltimore, Md. : 1950) 320 17475874
2006 RNA- and virus-independent inhibition of antiviral signaling by RNA helicase LGP2. Journal of virology 237 17020950
2014 The innate immune sensor LGP2 activates antiviral signaling by regulating MDA5-RNA interaction and filament assembly. Molecular cell 216 25127512
2011 Expression and functional characterization of the RIG-I-like receptors MDA5 and LGP2 in Rainbow trout (Oncorhynchus mykiss). Journal of virology 183 21680521
2011 Chicken cells sense influenza A virus infection through MDA5 and CARDIF signaling involving LGP2. Journal of virology 164 22072756
2009 Solution structures of cytosolic RNA sensor MDA5 and LGP2 C-terminal domains: identification of the RNA recognition loop in RIG-I-like receptors. The Journal of biological chemistry 163 19380577
2009 Regulation of signal transduction by enzymatically inactive antiviral RNA helicase proteins MDA5, RIG-I, and LGP2. The Journal of biological chemistry 142 19211564
2009 The regulatory domain of the RIG-I family ATPase LGP2 senses double-stranded RNA. Nucleic acids research 123 19208642
2009 The RIG-I-like receptor LGP2 recognizes the termini of double-stranded RNA. The Journal of biological chemistry 121 19278996
2016 Structural Analysis of dsRNA Binding to Anti-viral Pattern Recognition Receptors LGP2 and MDA5. Molecular cell 120 27203181
2012 Paramyxovirus V proteins interact with the RNA Helicase LGP2 to inhibit RIG-I-dependent interferon induction. Journal of virology 115 22301134
2018 The RIG-I-like receptor LGP2 inhibits Dicer-dependent processing of long double-stranded RNA and blocks RNA interference in mammalian cells. The EMBO journal 107 29351913
2012 The RIG-I-like receptor LGP2 controls CD8(+) T cell survival and fitness. Immunity 106 22841161
2009 A shared interface mediates paramyxovirus interference with antiviral RNA helicases MDA5 and LGP2. Journal of virology 106 19403670
2015 LGP2 synergy with MDA5 in RLR-mediated RNA recognition and antiviral signaling. Cytokine 102 25794939
2014 Identification of an LGP2-associated MDA5 agonist in picornavirus-infected cells. eLife 102 24550253
2014 MDA5 and LGP2: accomplices and antagonists of antiviral signal transduction. Journal of virology 100 24850739
2014 RIG-I-like receptor LGP2 protects tumor cells from ionizing radiation. Proceedings of the National Academy of Sciences of the United States of America 81 24434553
2010 Evolutional conservation of molecular structure and antiviral function of a viral RNA receptor, LGP2, in Japanese flounder, Paralichthys olivaceus. Journal of immunology (Baltimore, Md. : 1950) 81 21098234
2013 LGP2 plays a critical role in sensitizing mda-5 to activation by double-stranded RNA. PloS one 77 23671710
2012 ATP hydrolysis enhances RNA recognition and antiviral signal transduction by the innate immune sensor, laboratory of genetics and physiology 2 (LGP2). The Journal of biological chemistry 77 23184951
2008 Structure and function of LGP2, a DEX(D/H) helicase that regulates the innate immunity response. The Journal of biological chemistry 75 18411269
2020 Viral RNA recognition by LGP2 and MDA5, and activation of signaling through step-by-step conformational changes. Nucleic acids research 72 33137199
2019 LGP2 binds to PACT to regulate RIG-I- and MDA5-mediated antiviral responses. Science signaling 61 31575732
2010 Identification and expression profiling analysis of grass carp Ctenopharyngodon idella LGP2 cDNA. Fish & shellfish immunology 57 20420913
2021 The RNA helicase DDX5 promotes viral infection via regulating N6-methyladenosine levels on the DHX58 and NFκB transcripts to dampen antiviral innate immunity. PLoS pathogens 56 33909701
2017 Nonencapsidated 5' Copy-Back Defective Interfering Genomes Produced by Recombinant Measles Viruses Are Recognized by RIG-I and LGP2 but Not MDA5. Journal of virology 49 28768856
2018 RNA sensor LGP2 inhibits TRAF ubiquitin ligase to negatively regulate innate immune signaling. EMBO reports 46 29661858
2022 RNA sensing via the RIG-I-like receptor LGP2 is essential for the induction of a type I IFN response in ADAR1 deficiency. The EMBO journal 42 35156720
2017 Laboratory of genetics and physiology 2 (LGP2) plays an essential role in hepatitis C virus infection-induced interferon responses. Hepatology (Baltimore, Md.) 41 28090671
2019 RNA Helicase LGP2 Negatively Regulates RIG-I Signaling by Preventing TRIM25-Mediated Caspase Activation and Recruitment Domain Ubiquitination. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 40 31237466
2017 Alternative Splicing Transcripts of Zebrafish LGP2 Gene Differentially Contribute to IFN Antiviral Response. Journal of immunology (Baltimore, Md. : 1950) 40 29203516
2018 Innate immune sensor LGP2 is cleaved by the Leader protease of foot-and-mouth disease virus. PLoS pathogens 38 29958302
2016 Negative regulation of the antiviral response by grouper LGP2 against fish viruses. Fish & shellfish immunology 37 27436518
2014 Paramyxovirus V protein interaction with the antiviral sensor LGP2 disrupts MDA5 signaling enhancement but is not relevant to LGP2-mediated RLR signaling inhibition. Journal of virology 36 24829334
2023 LGP2 Promotes Type I Interferon Production To Inhibit PRRSV Infection via Enhancing MDA5-Mediated Signaling. Journal of virology 34 36622220
2020 RIG-I-Like Receptor LGP2 Is Required for Tumor Control by Radiotherapy. Cancer research 34 33087322
2017 PUM1 is a biphasic negative regulator of innate immunity genes by suppressing LGP2. Proceedings of the National Academy of Sciences of the United States of America 34 28760986
2012 LGP2 downregulates interferon production during infection with seasonal human influenza A viruses that activate interferon regulatory factor 3. Journal of virology 34 22837208
2011 Impaired cellular responses to cytosolic DNA or infection with Listeria monocytogenes and vaccinia virus in the absence of the murine LGP2 protein. PloS one 33 21533147
2016 Molecular characterization and expression analyses of three RIG-I-like receptor signaling pathway genes (MDA5, LGP2 and MAVS) in Larimichthys crocea. Fish & shellfish immunology 30 27346150
2007 Regulation of interferon production by RIG-I and LGP2: a lesson in self-control. Science's STKE : signal transduction knowledge environment 30 17473309
2014 Protective role of LGP2 in influenza virus pathogenesis. The Journal of infectious diseases 29 24493823
2012 Amino acid requirements for MDA5 and LGP2 recognition by paramyxovirus V proteins: a single arginine distinguishes MDA5 from RIG-I. Journal of virology 27 23269789
2017 The antiviral signaling mediated by black carp MDA5 is positively regulated by LGP2. Fish & shellfish immunology 26 28526571
2013 RIG-I-like receptors evolved adaptively in mammals, with parallel evolution at LGP2 and RIG-I. Journal of molecular biology 26 24211720
2021 Efficient Dicer processing of virus-derived double-stranded RNAs and its modulation by RIG-I-like receptor LGP2. PLoS pathogens 25 34343211
2021 Immune regulator LGP2 targets Ubc13/UBE2N to mediate widespread interference with K63 polyubiquitination and NF-κB activation. Cell reports 25 34965427
2022 Effect of variants in LGP2 on MDA5-mediated activation of interferon response and suppression of hepatitis D virus replication. Journal of hepatology 24 36152765
2016 LGP2 of black carp plays an important role in the innate immune response against SVCV and GCRV. Fish & shellfish immunology 24 27539705
2020 LGP2 virus sensor enhances apoptosis by upregulating apoptosis regulatory genes through TRBP-bound miRNAs during viral infection. Nucleic acids research 22 31799626
2018 Molecular characterization and function analysis of three RIG-I-like receptor signaling pathway genes (MDA5, LGP2 and MAVS) in Oreochromis niloticus. Fish & shellfish immunology 22 30099139
2018 Virus Sensor RIG-I Represses RNA Interference by Interacting with TRBP through LGP2 in Mammalian Cells. Genes 22 30347765
2017 PACT is required for MDA5-mediated immunoresponses triggered by Cardiovirus infection via interaction with LGP2. Biochemical and biophysical research communications 20 29032202
2014 LGP2 plays extensive roles in modulating innate immune responses in Ctenopharyngodon idella kidney (CIK) cells. Developmental and comparative immunology 20 25450904
2024 Unraveling blunt-end RNA binding and ATPase-driven translocation activities of the RIG-I family helicase LGP2. Nucleic acids research 18 38015453
2020 An Alternative Splicing of Tupaia STING Modulated Anti-RNA Virus Responses by Targeting MDA5-LGP2 and IRF3. Journal of immunology (Baltimore, Md. : 1950) 17 32376647
2015 Molecular cloning and immune responsive expression of LGP2 gene, a pivotal member of the RLR gene family from Muscovy duck Cairina moschata. Poultry science 17 25840960
2016 The evolution and functional characterization of miiuy croaker cytosolic gene LGP2 involved in immune response. Fish & shellfish immunology 16 27637730
2013 Genetic structure, polymorphism identification of LGP2 gene and their relationship with the resistance/susceptibility to GCRV in grass carp, Ctenopharyngodon idella. Gene 16 23506828
2014 CpG methylation in the 5'-flanking region of LGP2 gene lacks association with resistance/susceptibility to GCRV but contributes to the differential expression between muscle and spleen tissues in grass carp, Ctenopharyngodon idella. Fish & shellfish immunology 15 24998981
2015 Evolutionary conservation of molecular structure and antiviral function of a viral receptor, LGP2, in amphioxus Branchiostoma japonicum. European journal of immunology 14 26442622
2021 Analysis of Porcine RIG-I Like Receptors Revealed the Positive Regulation of RIG-I and MDA5 by LGP2. Frontiers in immunology 13 34093517
2019 LGP2 plays a critical role in MDA5-mediated antiviral activity against duck enteritis virus. Molecular immunology 13 31675523
2023 Infectious bronchitis virus nucleocapsid protein suppressed type I interferon production by interfering with the binding of MDA5-dsRNA and interacting with LGP2. Veterinary microbiology 12 37307767
2018 MDA5 and LGP2 acts as a key regulator though activating NF-κB and IRF3 in RLRs signaling of mandarinfish. Fish & shellfish immunology 12 30594581
2017 Identification, ontogeny and expression analysis of a novel laboratory of genetics and physiology 2 (LGP2) transcript in Asian seabass, Lates calcarifer. Fish & shellfish immunology 12 28119144
2012 LGP2 expression is enhanced by interferon regulatory factor 3 in olive flounder, Paralichthys olivaceus. PloS one 12 23251565
2024 Contrasting functions of ATP hydrolysis by MDA5 and LGP2 in viral RNA sensing. The Journal of biological chemistry 11 38309507
2021 Presence of two RIG-I-like receptors, MDA5 and LGP2, and their dsRNA binding capacity in a perciform fish, the snakehead Channa argus. Developmental and comparative immunology 9 34418428
2016 Cloning, characterization, and expression analysis of LGP2 cDNA from goose, Anser cygnoides. Poultry science 9 27143779
2022 K63-linked polyubiquitination of LGP2 by Riplet regulates RIG-I-dependent innate immune response. EMBO reports 8 36515138
2024 MATR3 promotes liver cancer progression by suppressing DHX58-mediated type I interferon response. Cancer letters 7 39276912
2022 Function conservation and disparities of zebrafish and human LGP2 genes in fish and mammalian cells responsive to poly(I:C). Frontiers in immunology 7 36059486
2022 Transcriptome analysis identifies LGP2 as an MDA5-mediated signaling activator following spring viremia of carp virus infection in common carp (Cyprinus carpio L.). Frontiers in immunology 7 36330521
2023 LGP2 directly interacts with flavivirus NS5 RNA-dependent RNA polymerase and downregulates its pre-elongation activities. PLoS pathogens 5 37656756
2023 Black carp LGP2 suppresses RIG-I mediated IFN signaling during the antiviral innate immunity. Fish & shellfish immunology 5 37944680
2022 The first identified invertebrate LGP2-like homolog gene in the Pacific oyster Crassostrea gigas. Fish & shellfish immunology 5 35940537
2022 A protocol to characterize zebrafish LGP2 as a dual regulator of IFN response during viral infection. STAR protocols 5 36595883
2020 Molecular characterization and expressional quantification of lgp2, a modulatory co-receptor of RLR-signalling pathway in the Indian major carp Labeo rohita following pathogenic challenges and PAMP stimulations. Journal of fish biology 5 32133636
2010 Expression patterns and association analysis of the porcine DHX58 gene. Animal genetics 5 20331611
2022 Duck LGP2 Downregulates RIG-I Signaling Pathway-Mediated Innate Immunity Against Tembusu Virus. Frontiers in immunology 4 35784309
2024 HOIL1 mediates MDA5 activation through ubiquitination of LGP2. bioRxiv : the preprint server for biology 3 38617308
2021 Regulation of MDA5-dependent anti-Tembusu virus innate immune responses by LGP2 in ducks. Veterinary microbiology 3 34785476
2025 Characterisation of LGP2 complex multitranscript system in humans: role in the innate immune response and evolution from non-human primates. Human molecular genetics 2 39505366
2026 Molecular mechanism of MDA5 nucleation and filament formation by LGP2. Molecular cell 1 41558484
2025 IHNV induced miR-19-3p modulates immune response of rainbow trout (Oncorhynchus mykiss) by targeting DHX58-dependent RLR signaling pathway. Fish & shellfish immunology 1 39954832
2025 Cytokine-independent induction of LGP2/DHX58 in viral infection. The Journal of general virology 1 41171864
2024 LGP2 Facilitates Bacterial Escape through Binding Peptidoglycan via EEK Motif and Suppressing NOD2-RIP2 Axis in Cyprinidae and Xenocyprididae Families. Journal of immunology (Baltimore, Md. : 1950) 1 38629918
2023 Genetic variants of IFIH1 and DHX58 affect the chronicity of hepatitis C in the Chinese Han population. PeerJ 1 36743960
2023 The RNA-Binding Proteins OAS1, ZFP36L2, and DHX58 Are Involved in the Regulation of CD44 mRNA Splicing in Colorectal Cancer Cells. Bulletin of experimental biology and medicine 1 37336810
2023 The role of duck LGP2 in innate immune response of host anti-tembusu virus. Veterinary microbiology 1 37951010
2026 Integrative genomic analysis reveals DHX58 as a key player in gastric cancer. PloS one 0 41569991
2026 Identification and optimization of first-in-class RNA helicase inhibitors of DDX1, LGP2, and MDA5. European journal of medicinal chemistry 0 41795418
2026 CRISPR/Cas9-mediated lgp2 knockout and cross-species rescue reveal the immunoregulatory role of LGP2 in zebrafish. Fish & shellfish immunology 0 41921842
2024 ANAX4 is a downstream molecule of LGP2 and promotes GCRV proliferation. Fish & shellfish immunology 0 39216711

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