Affinage

GBP2

Guanylate-binding protein 2 · UniProt P32456

Length
591 aa
Mass
67.2 kDa
Annotated
2026-06-10
59 papers in source corpus 30 papers cited in narrative 30 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

GBP2 is an interferon-inducible large GTPase whose two best-evidenced roles are nuclear mRNA surveillance/export in yeast and cell-autonomous innate immune defense in mammals (PMID:24452287, PMID:37023136). In yeast, Gbp2 is cotranscriptionally loaded onto nascent mRNPs: it associates with the TREX/THO complex and the elongation kinase Ctk1, and structural work shows its RRM1/RRM2 domains read a GGUG RNA motif while its non-RNA-binding RRM3 docks onto THO, which acts as a landing pad that configures Gbp2 for mRNP loading (PMID:14769921, PMID:26602689, PMID:33787496). Once loaded, Gbp2 functions as a splicing quality-control factor that retains unspliced transcripts, stabilizes TRAMP-directed exosomal degradation of faulty RNAs, and recruits the export receptor Mex67 for correctly spliced messages, with its shuttling controlled by the import receptor Mtr10 and kinase Sky1 (PMID:12634846, PMID:24452287). It extends repression into the cytoplasm by binding eIF4G1 through its RGG motif to inhibit translation and by localizing to stress granules (PMID:33910495). In mammals, the gene is transcriptionally activated by sequential STAT1- and IRF1-dependent chromatin remodeling at its promoter, and the protein is geranylgeranylated via a C-terminal CaaX motif (PMID:17293456, PMID:9858320). GBP2 drives the non-canonical inflammasome by directly polymerizing and aggregating free LPS to potentiate caspase-4 activation, and its intracellular localization is governed by autophagic flux downstream of IRGM proteins (PMID:37023136, PMID:21757726). In tumor biology GBP2 undergoes IDR-dependent phase separation to sequester the phosphatase SHP1, sustaining STAT1 activation, suppressing SLC7A11 and sensitizing cells to ferroptosis (PMID:41444224), and competes with SHP1 for STAT1 binding to enhance IFN-γ responses (PMID:35383115). Under Parkinsonian stress, geranylgeranylated GBP2 accumulates at mitochondria, binds the mitophagy receptor NIX via its large GTPase domain, and targets NIX for proteasomal degradation to suppress mitophagy (PMID:41570768). Across multiple settings GBP2 also modulates inflammasome and pyroptosis pathways (NLRP3, AIM2, GSDMD) and Rho/STAT-dependent cancer cell migration (PMID:42115407, PMID:41563239, PMID:34830789).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2003 Medium

    Established that yeast Gbp2 is a shuttling poly(A)+ RNA-binding protein whose nucleocytoplasmic cycling is coupled to mRNA export, defining it as an mRNP-associated trafficking factor rather than a static nuclear protein.

    Evidence Genetic deletion (mtr10Δ, sky1Δ) with poly(A)+ RNA localization and export-dependency assays in yeast

    PMID:12634846

    Open questions at the time
    • Did not define the RNA sequence specificity
    • Mechanism of cargo loading onto nascent transcripts not addressed
  2. 2004 High

    Showed Gbp2 is recruited cotranscriptionally via the TREX complex and the CTD kinase Ctk1, linking its mRNP loading to active transcription elongation.

    Evidence Co-IP with TREX components, RIP, and ChIP across transcribed genes in yeast

    PMID:14769921

    Open questions at the time
    • Domain responsible for THO/TREX contact not yet mapped
    • Functional consequence for the loaded mRNA not defined
  3. 2007 High

    Defined how the mammalian gbp2 gene is induced, showing a two-step STAT1-then-IRF1 chromatin-remodeling mechanism that licenses transcription.

    Evidence ChIP in stat1−/− and irf1−/− cells, STAT1-S727A mutant, and IRF1–Pol II Co-IP

    PMID:17293456

    Open questions at the time
    • Does not address GBP2 protein function
    • Upstream signals beyond IFN-γ not explored
  4. 1998 Medium

    Demonstrated murine GBP-2 is geranylgeranylated through a C-terminal CaaX motif, identifying a lipid modification that would later prove decisive for membrane targeting.

    Evidence [3H]mevalonate metabolic labeling and subcellular fractionation in COS cells

    PMID:9858320

    Open questions at the time
    • Functional role of prenylation not established at the time
    • Conditions driving membrane recruitment unknown
  5. 2014 High

    Established Gbp2 as a splicing quality-control surveillance factor that retains unspliced transcripts, directs faulty RNAs to the exosome via TRAMP, and licenses export of correct mRNAs via Mex67.

    Evidence Deletion strains with in situ hybridization for pre-mRNA leakage, RIP, and Co-IP with spliceosome/TRAMP/Mex67 in yeast

    PMID:24452287

    Open questions at the time
    • How the splicing status is sensed molecularly not resolved
    • Generality across all intron-containing genes not quantified
  6. 2015 High

    Resolved the structural basis of Gbp2 function, showing RRM1/RRM2 bind a GGUG motif while RRM3 instead mediates THO/TREX docking, separating RNA recognition from complex assembly.

    Evidence NMR structures of RRM1/RRM2/RRM3, RNA-binding assays, mutagenesis, and gbp2/tho2 genetic epistasis in yeast

    PMID:26602689

    Open questions at the time
    • Architecture of the full mRNP-bound complex not visualized
    • Coordination between RNA binding and THO docking in vivo not timed
  7. 2021 High

    Provided a structural model in which THO serves as a landing pad that configures Gbp2 for mRNP loading, integrating both its RS and RRM domains.

    Evidence 3.7 Å cryo-EM of the THO•Sub2 complex with cross-linking mass spectrometry mapping THO–Gbp2 contacts

    PMID:33787496

    Open questions at the time
    • Conformational changes upon Gbp2 release not captured
    • Transfer step from THO to mature mRNP not visualized
  8. 2021 Medium

    Extended Gbp2 function into the cytoplasm, showing it directly represses translation through eIF4G1 binding via its RGG motif and partitions into stress granules.

    Evidence eIF4G1 pull-down, in vivo tethering reporter, in vitro translation, polysome fractionation, and stress-granule imaging in yeast

    PMID:33910495

    Open questions at the time
    • Selectivity for specific mRNAs unknown
    • Link between nuclear surveillance and cytoplasmic repression not mechanistically closed
  9. 2011 Medium

    Showed that mammalian Gbp2 intracellular localization is controlled indirectly by IRGM proteins through autophagic flux rather than direct binding.

    Evidence LC3/p62 co-localization in Irgm1/Irgm3- and Atg5-deficient cells with a negative Irgm3–Gbp2 Co-IP

    PMID:21757726

    Open questions at the time
    • Direct autophagy machinery interactor not identified
    • Functional consequence of mislocalization for pathogen defense not quantified
  10. 2016 Medium

    Demonstrated GBP2 is targeted to pathogen-containing vacuoles and that a pathogen actively counteracts this, framing GBP2 as a cell-autonomous anti-parasite effector.

    Evidence ROP54 disruption in T. gondii with immunofluorescence of GBP2/IRGb6 PVM loading and virulence assays

    PMID:27303719

    Open questions at the time
    • Molecular determinant of GBP2 vacuolar loading not defined
    • Mechanism by which ROP54 blocks loading unknown
  11. 2023 High

    Defined a direct biochemical mechanism for GBP2 in innate immunity: it polymerizes to aggregate free LPS and potentiate caspase-4 non-canonical inflammasome activation.

    Evidence In vitro LPS aggregation and reconstituted caspase-4 activation with recombinant proteins, plus GBP1KO complementation

    PMID:37023136

    Open questions at the time
    • Structural basis of GBP2 polymerization not resolved
    • Relative contribution of GBP1 vs GBP2 in cells not fully partitioned
  12. 2025 High

    Established a mitochondrial role for prenylated GBP2: it binds the mitophagy receptor NIX and drives its proteasomal degradation, suppressing mitophagy and promoting neuronal apoptosis.

    Evidence Co-IP with domain mapping (large GTPase domain), ubiquitination assay, NIX-knockdown epistasis, and GGTI298 in an MPTP mouse model

    PMID:41570768

    Open questions at the time
    • E3 ligase mediating NIX degradation not identified
    • Whether GTPase activity is required not tested
  13. 2025 High

    Showed GBP2 phase separation sequesters SHP1 to sustain STAT1 signaling and sensitize tumors to ferroptosis, linking a condensate mechanism to immune-driven tumor control.

    Evidence IDR-dependent condensate assays, SHP1 Co-IP, STAT1/SLC7A11/HMGB1 readouts, and in vivo T-cell tumor models

    PMID:41444224

    Open questions at the time
    • Trigger for condensate dissolution not defined
    • Relationship to GBP2 GTPase or prenylation states unexplored
  14. 2025 Medium

    Identified direct GBP2–GSDMD binding that blocks non-pyroptotic GSDMD-driven YAP nuclear translocation, expanding GBP2 immune-surveillance roles into chemokine control.

    Evidence GBP2–GSDMD Co-IP, GSDMD cleavage and YAP localization assays, CXCL9/10/11 transcription, patient samples and mouse models

    PMID:42115407

    Open questions at the time
    • Binding interface on GSDMD not mapped
    • How binding inhibits cleavage mechanistically not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how GBP2's GTPase activity, prenylation, polymerization, and phase-separation behaviors are mechanistically coordinated to switch between its mRNA-surveillance, anti-pathogen, mitochondrial, and tumor-signaling functions.
  • No unified structural/biochemical model across functions
  • Role of nucleotide state in mammalian functions untested
  • Substrate/partner determinants of context-specific behavior unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 3 GO:0098772 molecular function regulator activity 2 GO:0140313 molecular sequestering activity 2 GO:0045182 translation regulator activity 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-168256 Immune System 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 2
Partners
EIF4G1GSDMDKIF22MEX67NIXOTUD5SHP1STAT1
Complex memberships
TREX/THO complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Gbp2 (yeast) is a shuttling poly(A)+ RNA-binding protein whose nuclear import depends on the receptor Mtr10 and the SR-specific kinase Sky1; deletion of MTR10 increases Gbp2 binding to poly(A)+ RNA in the cytoplasm, suggesting Mtr10 facilitates Gbp2 dissociation from mRNA upon cytoplasmic arrival. Nuclear export of Gbp2 is coupled to mRNA export and requires continuous RNA Pol II transcription and mRNA-export factors. Genetic deletion (mtr10Δ, sky1Δ), poly(A)+ RNA localization assays, nuclear export dependency experiments EMBO reports Medium 12634846
2004 Yeast Gbp2 (and Hrb1) are specifically associated with the TREX complex and interact with Ctk1 (the kinase that phosphorylates the RNA Pol II CTD during elongation), leading to cotranscriptional recruitment of Gbp2 to nascent mRNA across actively transcribed gene lengths. Co-immunoprecipitation with TREX components, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP) Proceedings of the National Academy of Sciences of the United States of America High 14769921
2007 Transcriptional activation of the gbp2 gene (mammalian) requires both STAT1 and IRF1. STAT1 (phosphorylated at S727) recruits CBP and HDAC1 to the gbp2 promoter and drives histone H4 hyperacetylation to create transcriptionally competent chromatin; IRF1 subsequently associates and directly contacts RNA Pol II to initiate transcription. A STAT1-S727A mutant strongly reduces CBP recruitment, H4 hyperacetylation, and RNA Pol II association at the gbp2 promoter. ChIP in WT, stat1−/−, irf1−/− cells; STAT1-S727A point-mutant analysis; Co-IP of IRF1 with RNA Pol II Proceedings of the National Academy of Sciences of the United States of America High 17293456
1998 Murine GBP-2 is prenylated via a C-terminal CaaX motif, preferentially incorporating the C-20 isoprenoid geranylgeraniol, as detected by [3H]mevalonate incorporation in COS cells; despite prenylation, mGBP-2 is primarily cytosolic. [3H]mevalonate metabolic labeling, subcellular fractionation Journal of interferon & cytokine research Medium 9858320
2011 IRGM proteins (Irgm1, Irgm3) indirectly regulate the intracellular localization of Gbp2 via macroautophagy; in Irgm1/Irgm3-deficient or Atg5-deficient cells, Gbp2 accumulates in LC3+ and p62/Sqstm1+ autophagic compartments. Co-IP showed Irgm3 does NOT directly interact with Gbp2, indicating the regulation is indirect through autophagic flux. Immunofluorescence co-localization with LC3/p62, co-immunoprecipitation (negative result for direct Irgm3–Gbp2 interaction), Atg5-KO cells The Journal of biological chemistry Medium 21757726
2014 Yeast Gbp2 (and Hrb1) bind pre-mRNAs and the spliceosome during splicing, acting as quality control surveillance factors that retain unspliced transcripts in the nucleus; they stabilize TRAMP complex binding to spliceosome-associated transcripts to target faulty RNAs to the nuclear exosome; upon splicing completion, they recruit the export receptor Mex67 to allow nuclear export of correctly spliced mRNAs. Genetic deletion (gbp2Δ, hrb1Δ) with in situ hybridization for unspliced pre-mRNA accumulation, RNA immunoprecipitation, co-immunoprecipitation with spliceosome/TRAMP/Mex67 Nature communications High 24452287
2015 NMR structures of Gbp2 RRM1 and RRM2 show preferential binding to RNA containing the GGUG core motif, with sequence selectivity residing in a non-canonical interface in RRM2 related to the SRSF1 pseudoRRM. The C-terminal RRM3 domain does not bind RNA/DNA due to N-terminal extensions blocking the canonical interface; instead, RRM3 is essential for interaction with the THO/TREX complex, and key residues for this interaction were identified. Genetic interaction: double deletion of gbp2 and tho2 shows synthetic phenotype, and preventing Gbp2–THO interaction partly suppresses gene expression defects caused by THO inactivation. NMR structure determination, RNA-binding assays, mutagenesis of key RRM3 residues, genetic epistasis (double deletion) Nucleic acids research High 26602689
2016 The Toxoplasma gondii rhoptry pseudokinase ROP54, injected into the host cytoplasm and localizing to the parasitophorous vacuole membrane, specifically suppresses host GBP2 loading onto the parasitophorous vacuole (but not IRGb6 loading), thereby promoting parasite immune evasion. Loss of ROP54 results in substantially increased GBP2 deposition on the vacuole. ROP54 disruption in type II T. gondii, immunofluorescence quantification of GBP2 and IRGb6 loading on PVM, macrophage clearance assay, in vivo virulence assay mSphere Medium 27303719
2018 Murine Gbp2 is ubiquitinated in a Toxoplasma gondii infection-independent manner, as detected by mass spectrometry using the di-glycine remnant method in IFNγ-stimulated murine embryonic fibroblasts. Mass spectrometry-based di-glycine remnant proteomics in MEFs BMC research notes Low 29510761
2021 Cryo-EM structure of the yeast THO•Sub2 complex at 3.7 Å reveals the THO complex assembly around Tho2 and stabilizes Sub2 in a semi-open conformation. THO interacts with the SR-like protein Gbp2 through both its RS domain and RRM domains; cross-linking mass spectrometry shows extensive THO–Gbp2 contacts with RRM domains near the Tho2 C-terminal domain, supporting a model where THO serves as a landing pad to configure Gbp2 for loading onto mRNP. Cryo-EM structure determination (3.7 Å), cross-linking mass spectrometry eLife High 33787496
2021 Yeast Gbp2 localizes to cytoplasmic stress granules upon heat shock and oxidative stress. Gbp2 directly binds the translation initiation factor eIF4G1 via its RGG motif; tethering Gbp2 to a reporter mRNA reduces its translation in vivo, and Gbp2 represses translation in in vitro translation systems in an RGG-motif-dependent manner. The RGG-motif deletion mutant is also defective in polysome association. Pull-down assays (Gbp2–eIF4G1 interaction), in vivo tethering reporter assay, in vitro translation assay, polysome fractionation, stress granule imaging RNA biology Medium 33910495
2021 Yeast Gbp2 (and Hrb1) extend quality control to the cytoplasm: they inhibit translation of exported transcripts and recruit cytoplasmic degradation factors to support nonsense-mediated decay (NMD), thereby linking nuclear splicing surveillance to cytoplasmic NMD. Genetic deletion with NMD reporter assays, biochemical fractionation (review/synthesis of prior experimental work from the lab) International journal of molecular sciences Low 34681934
2023 GBP2 (human) directly binds and aggregates free LPS through protein polymerization; recombinant polymerized GBP2 is sufficient to enhance LPS-induced caspase-4 activation in a reconstituted in vitro reaction, independent of direct bacterial surface binding. GBP2 cannot bind bacteria on its own but requires GBP1; nonetheless, LPS aggregation by GBP2 is sufficient to promote non-canonical inflammasome activation. In vitro LPS aggregation assay, reconstituted caspase-4 activation assay with recombinant proteins, GBP1KO cell complementation experiments, GBP1 triple-arginine motif mutant analysis Proceedings of the National Academy of Sciences of the United States of America High 37023136
2020 GBP2 promotes GBM cell migration and invasion through a GBP2→Stat3→fibronectin (FN1) signaling cascade: GBP2 induces FN1 expression at both mRNA and protein levels, Stat3 pathway inhibition blocks GBP2-driven FN1 induction and invasion, and FN1 is required for GBP2-promoted invasiveness in vitro and in vivo. RNA interference (GBP2 knockdown/overexpression), Stat3 inhibitor treatment, in vitro migration/invasion assay, mouse intracranial tumor model Oncogene Medium 32518375
2021 GBP-2 (murine) inhibits breast cancer cell migration and invadosome formation by regulating Rho family GTPases downstream; GBP-2 expression is inversely correlated with aggressiveness in 4T1 vs. 67NR cells, and altered GBP-2 expression levels modulate migration and invadosome formation without affecting proliferation. GBP-2 expression alteration in 4T1/67NR cell lines, proliferation assay, migration assay, invadosome formation assay, Rho GTPase activity assessment Cancers Medium 34830789
2022 GBP2 facilitates glioma progression through direct interaction with KIF22, which regulates EGFR signaling; GBP2 depletion impairs proliferation and migration in glioma cells, while overexpression enhances these processes in vitro and in vivo. Co-immunoprecipitation (GBP2–KIF22 interaction), siRNA knockdown, overexpression, in vitro proliferation/migration assays, in vivo tumor model Cell death discovery Medium 35436989
2022 GBP2 promotes STAT1 phosphorylation by competing with SHP1 for binding to STAT1 in MSS colorectal cancer cells; reduced GBP2 expression inhibits antigen processing/presentation machinery and CXCL10/11 expression upon IFN-γ stimulation, and decreases CD8+ T cell migration. Co-immunoprecipitation (GBP2 vs. SHP1 competition for STAT1 binding), GBP2 knockout, Transwell CD8+ T cell migration assay, CXCL10/11 measurement Journal for immunotherapy of cancer Medium 35383115
2023 GBP2 in macrophage-derived exosomes (L-Exo) activates NLRP3 inflammasome signaling as a direct target in alveolar epithelial cells, inducing epithelial cell dysfunction and pyroptosis; GBP2 inhibition in vivo and in vitro reverses these effects, while GBP2 overexpression promotes them. GBP2 siRNA knockdown and overexpression in macrophages, exosome transfer to epithelial cells, NLRP3 inflammasome activation assay, in vivo ALI model International immunopharmacology Low 37812968
2023 GBP2 promotes M1 macrophage polarization by activating the Notch1 signaling pathway in the context of diabetic nephropathy. GBP2 knockdown/overexpression in macrophages, Notch1 pathway analysis, M1 polarization markers, in vitro and in vivo validation Frontiers in immunology Low 37622120
2024 GBP2 interacts directly with OTUD5 (a deubiquitinase), and this interaction promotes GPX4 ubiquitination and degradation, driving ferroptosis in pulmonary vascular endothelial cells. EV-packaged GBP2 from macrophages transfers this pro-ferroptotic activity to endothelial cells. The small molecule Plantainoside D binds GBP2 and inhibits the GBP2–OTUD5 interaction, reducing GPX4 ubiquitination. RNA interference, adeno-associated virus transfection, endothelial-specific Gpx4 KO mice, cellular thermal shift assay, molecular docking, Co-immunoprecipitation (GBP2–OTUD5), ubiquitination assay for GPX4 Redox biology Medium 40156957
2024 In triple-negative breast cancer cells, GBP2 promotes autophagy by co-acting with ATG2 (fluorescence co-localization) and inhibiting the PI3K/AKT/mTOR pathway, thereby enhancing paclitaxel sensitivity; autophagy inhibition reverses GBP2-driven PTX sensitization. Lentiviral GBP2 overexpression, immunoblotting, transmission electron microscopy, fluorescence co-localization (GBP2–ATG2), PI3K/AKT/mTOR pathway analysis, autophagy inhibitor rescue experiment, mouse xenograft model International journal of oncology Low 38334171
2025 PD-related stress promotes GBP2 geranylgeranylation, driving its accumulation at mitochondria where it directly binds the mitophagy receptor NIX via its large GTPase domain; GBP2 then targets NIX for ubiquitin-proteasomal degradation, suppressing NIX-mediated mitophagy and promoting dopaminergic neuron apoptosis. Pharmacological inhibition of geranylgeranylation (GGTI298) attenuates MPTP-induced neurotoxicity. GBP2 knockdown neuroprotection is abolished by mitophagy inhibition or NIX knockdown, establishing a linear pathway. Co-immunoprecipitation (GBP2–NIX), domain mapping (large GTPase domain), ubiquitination/proteasomal degradation assay, GBP2 knockdown in vivo (MPTP mouse model) and in vitro, GGTI298 pharmacological treatment, NIX knockdown epistasis Redox biology High 41570768
2025 Upon IFN-γ stimulation, GBP2 undergoes phase separation through an intrinsically disordered region, forming condensates that sequester SHP1 and sustain STAT1 activation, thereby suppressing SLC7A11 and sensitizing tumor cells to ferroptotic death. GBP2 also increases HMGB1 release from ferroptotic cells to promote CD8+ T cell infiltration. Disrupting GBP2 phase separation impairs ferroptosis and weakens T cell-driven tumor control. Phase separation assays (IDR-dependent condensate formation), Co-IP (GBP2 sequesters SHP1), STAT1 phosphorylation analysis, SLC7A11 expression analysis, HMGB1 release assay, in vivo tumor model with T cell analysis Nature communications High 41444224
2025 ATF4 promotes tubular epithelial cell pyroptosis in drug-induced AKI by activating STAT1 phosphorylation; STAT1 then interacts with GBP2 to drive NLRP3 inflammasome activation. ATF4 suppression inhibits STAT1 phosphorylation and disrupts the STAT1–GBP2 interaction, attenuating NLRP3 activation and pyroptosis. Co-immunoprecipitation (STAT1–GBP2), luciferase reporter assay, ATF4 conditional KO mice, Western blotting, RNA sequencing Journal of the American Society of Nephrology Medium 41563239
2025 GBP2 suppresses MLV replication by inhibiting furin protease, which is required to cleave the viral envelope glycoprotein (Env) at the SU-TM cleavage site. GBP2 sensitivity and furin dependence are determined by the amino acid sequence at the SU-TM cleavage site; substitution of ecotropic Moloney cleavage site sequence with XMRV sequence confers resistance to both GBP2 and furin silencing, and the reverse substitution confers sensitivity. Furin silencing, GBP2 overexpression in MLV infection assay, cleavage site sequence substitution mutagenesis in Env International journal of molecular sciences Medium 39337476
2025 GBP2 directly binds GSDMD (gasdermin D), inhibiting its cleavage-dependent activation and preventing non-pyroptotic GSDMD-driven YAP nuclear translocation; nuclear YAP represses CXCL9/10/11 transcription and limits CD8+ T cell infiltration. GBP2 thus maintains YAP in its inactive cytoplasmic state and enhances immune surveillance. Co-immunoprecipitation (GBP2–GSDMD direct binding), GSDMD cleavage assays, YAP localization analysis, CXCL9/10/11 transcription assays, genetic and pharmacological GSDMD inhibition, patient samples and mouse models Oncogene Medium 42115407
2025 Scutellarin inhibits LPS-induced M1 macrophage polarization by downregulating GBP2, which suppresses JAK2/STAT3 signaling; co-immunoprecipitation and molecular docking confirm a direct interaction between GBP2 and STAT3. GBP2 knockdown reduces and overexpression enhances LPS-induced M1 polarization markers. Co-immunoprecipitation (GBP2–STAT3), molecular docking, GBP2 siRNA knockdown and overexpression, LPS-induced ALI mouse model, RNA-seq Phytotherapy research Low 40968089
2025 Pro-apoptotic proteins Bak and Bax act as positive regulators that amplify the Gbp2-caspase-11 axis during pyroptosis induced by Vibrio vulnificus and Salmonella Typhimurium: Bak-/- and Bax-/- MEFs exhibit significantly reduced Gbp2 upregulation and caspase-11 activation, whereas MCL-1 overexpression does not affect Gbp2 expression or caspase-11 activation. Bak-/- and Bax-/- MEFs, MCL-1 overexpression, caspase-11 activation assay, LDH release assay, membrane integrity assay Journal of microbiology Medium 41025249
2025 GBP2 promotes nanovaccine-driven M1 macrophage polarization (TAM reprogramming) in ovarian cancer through the GBP2–Pin1–NFκB pathway: elevated GBP2 recruits Pin1, activating NFκB signaling, driving M1 polarization and tumor growth inhibition; targeting Gbp2 diminishes nanovaccine antitumor efficacy in vivo. RNA-seq, single-cell RNA-seq, mass spectrometry proteomics, GBP2 targeting in vivo, Pin1 recruitment assay Advanced science Low 39985265
2026 GBP2 promotes podocyte pyroptosis in lupus nephritis via the AIM2 pathway: Gbp2 knockdown reduces GSDMD, AIM2, Caspase-1 expression and IL-1β/IL-18 secretion, while overexpression aggravates these effects; pyroptosis suppression by Gbp2 knockdown is partially restored by concurrent AIM2 overexpression, establishing GBP2 upstream of AIM2-mediated pyroptosis. siRNA knockdown and overexpression of Gbp2, AIM2 overexpression rescue experiment, western blotting for pyroptosis markers, ELISA for IL-1β/IL-18 PloS one Medium 41855126

Source papers

Stage 0 corpus · 59 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Cotranscriptional recruitment of the serine-arginine-rich (SR)-like proteins Gbp2 and Hrb1 to nascent mRNA via the TREX complex. Proceedings of the National Academy of Sciences of the United States of America 116 14769921
2007 Distinct modes of action applied by transcription factors STAT1 and IRF1 to initiate transcription of the IFN-gamma-inducible gbp2 gene. Proceedings of the National Academy of Sciences of the United States of America 100 17293456
2014 Quality control of spliced mRNAs requires the shuttling SR proteins Gbp2 and Hrb1. Nature communications 86 24452287
2020 GBP2 enhances glioblastoma invasion through Stat3/fibronectin pathway. Oncogene 76 32518375
2011 Immunity-related GTPase M (IRGM) proteins influence the localization of guanylate-binding protein 2 (GBP2) by modulating macroautophagy. The Journal of biological chemistry 71 21757726
2023 LPS-aggregating proteins GBP1 and GBP2 are each sufficient to enhance caspase-4 activation both in cellulo and in vitro. Proceedings of the National Academy of Sciences of the United States of America 56 37023136
2022 Subtyping of microsatellite stability colorectal cancer reveals guanylate binding protein 2 (GBP2) as a potential immunotherapeutic target. Journal for immunotherapy of cancer 56 35383115
2019 TCR Affinity Biases Th Cell Differentiation by Regulating CD25, Eef1e1, and Gbp2. Journal of immunology (Baltimore, Md. : 1950) 56 30858199
2003 Identification of Gbp2 as a novel poly(A)+ RNA-binding protein involved in the cytoplasmic delivery of messenger RNAs in yeast. EMBO reports 52 12634846
1998 Murine GBP-2: a new IFN-gamma-induced member of the GBP family of GTPases isolated from macrophages. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 33 9858320
2023 GBP2 promotes M1 macrophage polarization by activating the notch1 signaling pathway in diabetic nephropathy. Frontiers in immunology 31 37622120
2021 Cryo-EM structure of the yeast TREX complex and coordination with the SR-like protein Gbp2. eLife 29 33787496
2008 Molecular characterization of the porcine GBP1 and GBP2 genes. Molecular immunology 29 18346789
2022 GBP2 facilitates the progression of glioma via regulation of KIF22/EGFR signaling. Cell death discovery 24 35436989
2017 Up-regulation of GBP2 is Associated with Neuronal Apoptosis in Rat Brain Cortex Following Traumatic Brain Injury. Neurochemical research 24 28239766
2016 The Rhoptry Pseudokinase ROP54 Modulates Toxoplasma gondii Virulence and Host GBP2 Loading. mSphere 23 27303719
2025 Extracellular vesicle-packaged GBP2 from macrophages aggravates sepsis-induced acute lung injury by promoting ferroptosis in pulmonary vascular endothelial cells. Redox biology 22 40156957
2018 Associations of GBP2 gene copy number variations with growth traits and transcriptional expression in Chinese cattle. Gene 21 29325733
2023 Dnmt1/Tet2-mediated changes in Cmip methylation regulate the development of nonalcoholic fatty liver disease by controlling the Gbp2-Pparγ-CD36 axis. Experimental & molecular medicine 19 36609599
2024 GBP2 enhances paclitaxel sensitivity in triple‑negative breast cancer by promoting autophagy in combination with ATG2 and inhibiting the PI3K/AKT/mTOR pathway. International journal of oncology 18 38334171
2022 6-Gingerol attenuates subarachnoid hemorrhage-induced early brain injury via GBP2/PI3K/AKT pathway in the rat model. Frontiers in pharmacology 18 36091803
2015 Gbp2 interacts with THO/TREX through a novel type of RRM domain. Nucleic acids research 18 26602689
2023 GBP2 upregulated in LPS-stimulated macrophages-derived exosomes accelerates septic lung injury by activating epithelial cell NLRP3 signaling. International immunopharmacology 17 37812968
2020 Plasma GBP2 promoter methylation is associated with advanced stages in breast cancer. Genetics and molecular biology 16 33211060
2021 Nuclear mRNA Quality Control and Cytoplasmic NMD Are Linked by the Guard Proteins Gbp2 and Hrb1. International journal of molecular sciences 14 34681934
2019 Unveiling the partners of the DRBD2-mRNP complex, an RBP in Trypanosoma cruzi and ortholog to the yeast SR-protein Gbp2. BMC microbiology 14 31185899
2022 Plasmodium falciparum GBP2 Is a Telomere-Associated Protein That Binds to G-Quadruplex DNA and RNA. Frontiers in cellular and infection microbiology 13 35273922
2019 C57BL/6 and 129 inbred mouse strains differ in Gbp2 and Gbp2b expression in response to inflammatory stimuli in vivo. Wellcome open research 13 31544161
2015 The genes Scgb1a1, Lpo and Gbp2 characteristically expressed in peri-implant epithelium of rats. Clinical oral implants research 12 25864924
2025 CpG-Based Nanovaccines Enhance Ovarian Cancer Immune Response by Gbp2-Mediated Remodeling of Tumor-Associated Macrophages. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 11 39985265
2022 GBP2 acts as a member of the interferon signalling pathway in lupus nephritis. BMC immunology 11 36115937
2022 Differential expression of interferon inducible protein: Guanylate binding protein (GBP1 & GBP2) in severe dengue. Free radical biology & medicine 11 36460216
2024 Crosstalk between GBP2 and M2 macrophage promotes the ccRCC progression. Cancer science 10 39222374
2021 RGG-motif containing mRNA export factor Gbp2 acts as a translation repressor. RNA biology 9 33910495
2019 Meta-Analysis of HTLV-1-Infected Patients Identifies CD40LG and GBP2 as Markers of ATLL and HAM/TSP Clinical Status: Two Genes Beat as One. Frontiers in genetics 8 31781157
2021 The Large GTPase, GBP-2, Regulates Rho Family GTPases to Inhibit Migration and Invadosome Formation in Breast Cancer Cells. Cancers 7 34830789
2024 GBP2 Regulates Lipid Metabolism by Inhibiting the HIF-1 Pathway to Alleviate the Progression of Allergic Rhinitis. Cell biochemistry and biophysics 6 39397223
2021 Roles and Cellular Localization of GBP2 and NAB2 During the Blood Stage of Malaria Parasites. Frontiers in cellular and infection microbiology 6 34604117
2024 CENPA facilitates glioma stem cell stemness and suppress ferroptosis to accelerate glioblastoma multiforme progression by promoting GBP2 transcription. Pathology, research and practice 5 38964117
2024 CD4+ Effective Memory T Cell Markers GBP2 and LAG3 Are Risk Factors for PTB and COVID-19 Infection: A Study Integrating Single-Cell Expression Quantitative Trait Locus and Mendelian Randomization Analyses. International journal of molecular sciences 5 39337460
2018 Murine Gbp1 and Gbp2 are ubiquitinated independent of Toxoplasma gondii infection. BMC research notes 4 29510761
2025 Novel insights into the molecular mechanisms of sepsis-associated acute kidney injury: an integrative study of GBP2, PSMB8, PSMB9 genes and immune microenvironment characteristics. BMC nephrology 3 40155864
2024 Drosophila cytokine GBP2 exerts immune responses and regulates GBP1 expression through GPCR receptor Mthl10. Insect biochemistry and molecular biology 3 38295885
2024 GBP2 inhibits pathological angiogenesis in the retina via the AKT/mTOR/VEGFA axis. Microvascular research 3 38636926
2026 Integrated Stress Response and Drug-Induced Acute Kidney Injury: Involvement of Activating ATF4-STAT1-GBP2 Signaling. Journal of the American Society of Nephrology : JASN 1 41563239
2026 Upregulated GBP2 exacerbates Parkinson's disease pathogenesis by impairing NIX-dependent mitophagy. Redox biology 1 41570768
2025 Interactions between particulate matter and bacteria during cowshed PM2.5-induced respiratory injury initiates GBP2/Caspase-11/NLRP3-mediated intracellular bacterial defense and pyroptosis. Frontiers in veterinary science 1 40697643
2025 Scutellarin Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Mice by Inhibiting M1 Macrophage Polarization via the GBP2/JAK2/STAT3 Signaling Pathway. Phytotherapy research : PTR 1 40968089
2026 GBP2 promotes podocyte pyroptosis and contributes to the pathogenesis of pediatric lupus nephritis. PloS one 0 41855126
2026 GBP2 enhances anti-PD-L1 response in colorectal cancer via GSDMD-mediated YAP nuclear translocation by non-pyroptotic. Oncogene 0 42115407
2025 [The research on the mechanism of GBP2 promoting the progression of silicosis by inducing macrophage polarization and epithelial cell transformation]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 0 40620118
2025 Bak and Bax are crucial for Gbp2-mediated pyroptosis during Vibrio and Salmonella infections. Journal of microbiology (Seoul, Korea) 0 41025249
2025 Downregulation of Gbp2 Attenuates LPS-Induced Inflammation in BV2 Microglia Cells Through Inhibition of STAT1. Journal of inflammation research 0 41080150
2025 Multi-omics and machine learning identify GBP2 as a key therapeutic target of Qingre Kasen granules in lupus nephritis via NF-kappaB modulation. Renal failure 0 41199598
2025 GBP2 regulates lung cancer progression through STAT1 and impacts glycolysis. Clinical and experimental medicine 0 41286130
2025 GBP2 condensates promote ferroptosis to sensitize anti-PD-L1 immunotherapy in melanoma. Nature communications 0 41444224
2024 The Furin Protease Dependence and Antiviral GBP2 Sensitivity of Murine Leukemia Virus Infection Are Determined by the Amino Acid Sequence at the Envelope Glycoprotein Cleavage Site. International journal of molecular sciences 0 39337476
2024 Gbp2 driving macrophages dynamics in murine heart transplant. Tissue & cell 0 39709712
2022 A reciprocal translocation involving Aspergillus nidulans snxAHrb1/Gbp2 and gyfA uncovers a new regulator of the G2-M transition and reveals a role in transcriptional repression for the setBSet2 histone H3-lysine-36 methyltransferase. Genetics 0 36005881

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