Affinage

GBP2

Guanylate-binding protein 2 · UniProt P32456

Length
591 aa
Mass
67.2 kDa
Annotated
2026-04-28
58 papers in source corpus 28 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GBP2 is a multifunctional interferon-γ-inducible large GTPase that operates in mRNA quality control (in yeast) and innate immune defense (in mammals). In Saccharomyces cerevisiae, Gbp2 is an SR-like shuttling RNA-binding protein cotranscriptionally loaded onto nascent mRNA via the TREX/THO complex through its RRM3 domain; it surveys splicing fidelity by recruiting TRAMP to defective transcripts for nuclear exosome degradation and loads the export receptor Mex67 onto correctly spliced mRNAs, while also functioning as a cytoplasmic translation repressor through RGG-motif-dependent binding of eIF4G1 (PMID:14769921, PMID:24452287, PMID:26602689, PMID:33910495). In mammalian innate immunity, human GBP2 polymerizes and aggregates free LPS to enhance caspase-4 activation and non-canonical inflammasome-driven pyroptosis, and promotes AIM2/GSDMD-dependent pyroptosis in additional contexts (PMID:37023136, PMID:41855126, PMID:41025249). GBP2 also undergoes IFN-γ-induced phase separation via an intrinsically disordered region to sequester the phosphatase SHP1, thereby sustaining STAT1 activation, suppressing SLC7A11, and sensitizing tumor cells to ferroptosis; separately, geranylgeranylation drives GBP2 mitochondrial translocation where it binds the mitophagy receptor NIX via its GTPase domain and promotes NIX proteasomal degradation, impairing mitophagy in dopaminergic neurons (PMID:41444224, PMID:41570768).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1998 Medium

    Establishing the post-translational modification status of GBP2: murine GBP-2 was shown to be geranylgeranylated at its C-terminal CaaX motif yet remain primarily cytosolic, raising the question of what triggers its membrane relocalization.

    Evidence Radiolabeled mevalonate incorporation in COS cells with subcellular fractionation

    PMID:9858320

    Open questions at the time
    • Stimulus or signal triggering membrane translocation was unknown
    • Whether prenylation is required for function was untested
    • Human GBP2 prenylation status not addressed
  2. 2003 High

    Defining yeast Gbp2 as a shuttling mRNA-binding protein whose nuclear-cytoplasmic transport depends on the import receptor Mtr10 and the SR kinase Sky1, establishing its identity as an SR-like protein coupled to mRNA export.

    Evidence Genetic deletion of MTR10, subcellular localization, poly(A)+ RNA binding assays in S. cerevisiae

    PMID:12634846

    Open questions at the time
    • How Gbp2 is loaded onto mRNA in the nucleus was unknown
    • Functional consequence of Gbp2 shuttling for mRNA fate was not defined
  3. 2004 High

    Resolving how Gbp2 is recruited to mRNA: cotranscriptional loading via the TREX complex and association with the CTD kinase Ctk1 showed that Gbp2 joins nascent transcripts during elongation, not post-transcriptionally.

    Evidence Co-IP, RNA-IP, and ChIP on actively transcribed genes in S. cerevisiae

    PMID:14769921

    Open questions at the time
    • Which domain of Gbp2 mediates TREX interaction was unresolved
    • Functional purpose of cotranscriptional loading (surveillance vs. export) was unclear
  4. 2007 High

    Defining the transcriptional regulation of the mammalian gbp2 gene: STAT1 S727 phosphorylation recruits CBP to the promoter, and IRF1 subsequently contacts RNA Pol II for productive transcription, establishing the two-step IFN-γ transcriptional activation mechanism.

    Evidence ChIP in WT, stat1−/−, and irf1−/− cells with STAT1-S727A mutagenesis

    PMID:17293456

    Open questions at the time
    • Whether this promoter architecture is shared by other GBP family members was not tested
    • Post-transcriptional regulation of GBP2 mRNA was not addressed
  5. 2014 High

    Establishing yeast Gbp2 as a nuclear mRNA quality-control factor: Gbp2 binds pre-mRNAs on the spliceosome, recruits TRAMP to target faulty transcripts for exosome degradation, and upon correct splicing loads the export receptor Mex67, gating mRNA export on splicing fidelity.

    Evidence RNA-IP, co-IP with spliceosome/TRAMP components, quantitative pre-mRNA export assays in deletion strains

    PMID:24452287

    Open questions at the time
    • How Gbp2 distinguishes correctly from incorrectly spliced transcripts at the molecular level was unclear
    • Whether Gbp2 surveils all intron-containing genes equally was not addressed
  6. 2015 High

    Structural basis of Gbp2 RNA recognition and TREX interaction: NMR structures revealed RRM1/2 bind GGUG-containing RNA while RRM3 does not bind RNA but instead mediates interaction with THO/TREX, resolving the domain-level division of labor.

    Evidence NMR structure determination, RNA binding assays, mutagenesis, genetic epistasis with Tho2 in S. cerevisiae

    PMID:26602689

    Open questions at the time
    • Full atomic-resolution structure of the Gbp2–THO complex was lacking
    • How RRM3–THO interaction is released after mRNP remodeling was unknown
  7. 2016 Medium

    Demonstrating that mammalian GBP2 is recruited to pathogen-containing vacuoles and is actively counteracted by pathogen effectors: T. gondii ROP54 specifically limits GBP2 loading onto the parasitophorous vacuole.

    Evidence ROP54-KO T. gondii, quantitative immunofluorescence of GBP2 loading on vacuoles in macrophages

    PMID:27303719

    Open questions at the time
    • Direct molecular target of ROP54 on GBP2 was not identified
    • Whether GBP2 vacuolar recruitment requires GTPase activity was untested
  8. 2021 High

    Cryo-EM of the THO•Sub2 complex confirmed that THO serves as a structural landing pad for Gbp2 loading, with cross-linking MS placing Gbp2 RRM domains near the Tho2 C-terminal domain, providing the first structural view of this interaction.

    Evidence Cryo-EM at 3.7 Å resolution with cross-linking mass spectrometry

    PMID:33787496

    Open questions at the time
    • A co-structure of THO bound to full-length Gbp2 was not obtained
    • Dynamics of Gbp2 handoff from THO to mRNA were not resolved
  9. 2021 High

    Expanding Gbp2 beyond nuclear surveillance to cytoplasmic translation repression: Gbp2 localizes to stress granules, directly binds eIF4G1 via its RGG motif, and represses translation both in vivo and in vitro, linking its nuclear and cytoplasmic mRNA regulatory roles.

    Evidence In vitro translation repression assay, tethering assay, RGG-motif deletion, pulldown with eIF4G1 in S. cerevisiae

    PMID:33910495

    Open questions at the time
    • Whether translation repression and stress granule localization are functionally separable was unclear
    • Physiological conditions activating cytoplasmic Gbp2 repression beyond heat shock were not fully defined
  10. 2022 Medium

    Revealing the mammalian GBP2–SHP1–STAT1 axis: GBP2 competes with phosphatase SHP1 for STAT1 binding, sustaining STAT1 phosphorylation and IFN-γ signaling in colorectal cancer cells.

    Evidence Co-IP of GBP2/SHP1/STAT1, GBP2 knockout, p-STAT1 western blot in microsatellite-stable CRC cells

    PMID:35383115

    Open questions at the time
    • Binding interface between GBP2 and STAT1 was not mapped
    • Whether GBP2 GTPase activity is required for SHP1 displacement was untested
  11. 2023 High

    Demonstrating that human GBP2 directly polymerizes and aggregates free LPS to enhance caspase-4 activation, establishing a GBP1-independent mechanism for non-canonical inflammasome engagement that does not require bacterial surface binding.

    Evidence In vitro caspase-4 activation with recombinant GBP2, LPS aggregation assay, GBP1-KO cell complementation

    PMID:37023136

    Open questions at the time
    • Structural basis of GBP2 polymerization on LPS was not resolved
    • Relative contributions of GBP2 vs. GBP1 to LPS sensing in physiological infection were not quantified
  12. 2025 High

    Multiple parallel advances defined new GBP2 effector mechanisms: (1) IFN-γ-induced phase separation via an intrinsically disordered region sequesters SHP1 to sustain STAT1 and drive ferroptosis; (2) geranylgeranylation drives mitochondrial translocation where GBP2 binds NIX and promotes its proteasomal degradation, impairing mitophagy in dopaminergic neurons; (3) GBP2 in macrophage-derived EVs binds OTUD5 to promote GPX4 ubiquitination and ferroptosis in endothelial cells; (4) GBP2 restricts MLV by inhibiting furin-mediated Env cleavage at the SU-TM junction.

    Evidence Phase separation/IDR mutagenesis with in vivo tumor models [PMID:41444224]; Co-IP of GBP2–NIX with GTPase domain mapping and MPTP mouse model [PMID:41570768]; Co-IP of GBP2–OTUD5 with GPX4 ubiquitination assay and endothelial-specific Gpx4-KO mice [PMID:40156957]; furin silencing and cleavage-site mutagenesis of MLV Env [PMID:39337476]

    PMID:39337476 PMID:40156957 PMID:41444224 PMID:41570768

    Open questions at the time
    • Whether phase separation and LPS polymerization activities are coordinated in infection is unknown
    • The GBP2–OTUD5 interaction domain has not been mapped
    • Whether NIX binding requires GTP hydrolysis or only GTP binding is unresolved
  13. 2025 Medium

    GBP2 was placed upstream of multiple pyroptosis pathways: it promotes caspase-11-mediated non-canonical pyroptosis downstream of Bak/Bax, and activates AIM2/GSDMD pyroptosis in podocytes; separately, ATF4 was identified as a transcriptional driver of GBP2 that promotes STAT1–GBP2 interaction and NLRP3-dependent pyroptosis.

    Evidence Bak/Bax-KO MEFs with caspase-11 assays [PMID:41025249]; AIM2 rescue experiment in podocytes [PMID:41855126]; ATF4-KO mice and STAT1–GBP2 Co-IP [PMID:41563239]

    PMID:41025249 PMID:41563239 PMID:41855126

    Open questions at the time
    • Whether GBP2 directly binds caspase-11 or acts through LPS aggregation in this context is unresolved
    • The direct molecular link between GBP2 and AIM2 activation has not been identified
    • Whether ATF4-driven GBP2 expression is relevant beyond drug-induced kidney injury is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions remain: what structural features of GBP2 underlie its polymerization on LPS, how its GTPase cycle controls effector switching between different immune outputs (pyroptosis, ferroptosis, mitophagy inhibition), and whether the phase separation mechanism operates during infection as well as in tumor immunity.
  • No high-resolution structure of human GBP2 polymer or GBP2–LPS complex
  • GTPase-cycle-dependent regulation of effector choice is undefined
  • Integration of nuclear mRNA surveillance function (yeast) with innate immune roles (mammalian) across evolution is unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 5 GO:0098772 molecular function regulator activity 3 GO:0003924 GTPase activity 2 GO:0045182 translation regulator activity 1 GO:0140313 molecular sequestering activity 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0005739 mitochondrion 1
Pathway
R-HSA-168256 Immune System 6 R-HSA-8953854 Metabolism of RNA 5 R-HSA-5357801 Programmed Cell Death 4 R-HSA-9612973 Autophagy 2 R-HSA-74160 Gene expression (Transcription) 1
Partners
EIF4G1MEX67NIXOTUD5SHP1STAT1THO2
Complex memberships
TREX/THO complex (yeast, recruited to)

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 Gbp2 (yeast SR-like protein) is cotranscriptionally recruited to nascent mRNA via association with the TREX complex and interacts with Ctk1, a kinase that phosphorylates the CTD of RNA Pol II during elongation; Gbp2 associates with actively transcribed genes and is bound to their transcripts. Co-immunoprecipitation, RNA immunoprecipitation, chromatin immunoprecipitation Proceedings of the National Academy of Sciences of the United States of America High 14769921
2003 Yeast Gbp2 is a shuttling poly(A)+ RNA-binding protein whose nuclear import depends on the receptor Mtr10 and the SR kinase Sky1; deletion of MTR10 shifts Gbp2 to the cytoplasm and increases its poly(A)+ RNA binding, indicating Mtr10 mediates dissociation of Gbp2 from mRNA in the cytoplasm; nuclear export of Gbp2 is coupled to mRNA export and requires RNA Pol II transcription. Genetic deletion, subcellular fractionation/localization, RNA-binding assay, overexpression toxicity assay EMBO reports High 12634846
2007 For IFN-γ-induced transcription of the gbp2 gene, STAT1 binds the promoter independently of IRF1 and recruits CBP/HDAC1 and drives histone H4 hyperacetylation; STAT1 S727 phosphorylation (in its transactivation domain) is required for CBP recruitment and RNA Pol II association; IRF1 binds subsequently and directly contacts RNA Pol II-containing complexes, being required for productive transcription initiation. ChIP in WT/stat1−/−/irf1−/− cells, STAT1-S727A mutant analysis, co-immunoprecipitation of IRF1 with RNA Pol II Proceedings of the National Academy of Sciences of the United States of America High 17293456
2014 Yeast Gbp2 and Hrb1 act as mRNA surveillance/quality-control factors: they bind pre-mRNAs and the spliceosome during splicing, are required for stable binding of the TRAMP complex to spliceosome-associated transcripts (targeting faulty RNAs to the nuclear exosome), and upon completion of correct splicing recruit the export receptor Mex67 to allow nuclear export; their absence causes leakage of unspliced pre-mRNAs into the cytoplasm. RNA immunoprecipitation, genetic deletion with quantitative pre-mRNA export assay, co-immunoprecipitation with spliceosome/TRAMP components Nature communications High 24452287
2011 IRGM proteins (Irgm1, Irgm3) indirectly regulate the intracellular localization of murine Gbp2 through modulation of autophagic flux; in the absence of Irgm1/Irgm3 or Atg5, Gbp2 accumulates in LC3+ and p62/Sqstm1+ autophagic compartments; Irgm3 does not directly co-immunoprecipitate with Gbp2 (unlike its interaction with Irgb6), indicating an indirect mechanism via autophagy regulation. Immunofluorescence co-localization, co-immunoprecipitation, Atg5-KO cells The Journal of biological chemistry Medium 21757726
1998 Murine GBP-2 is prenylated via its 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. Radiolabeled mevalonate incorporation assay, subcellular fractionation Journal of interferon & cytokine research Medium 9858320
2021 Cryo-EM structure of the yeast THO•Sub2 complex at 3.7 Å resolution reveals THO stabilizes a semi-open conformation of the Sub2 ATPase via Tho2 interactions; THO interacts with the SR-like protein Gbp2 through both its RS domain and RRM domains, with cross-linking mass spectrometry showing RRM domains of Gbp2 are proximal to the Tho2 C-terminal domain, suggesting THO serves as a landing pad to configure Gbp2 for mRNP loading. Cryo-EM structure determination, cross-linking mass spectrometry eLife High 33787496
2015 NMR structures of Gbp2 RRM1 and RRM2 show they preferentially bind RNAs containing the core motif GGUG, 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 its N-terminal extension blocking the canonical binding interface, but instead mediates interaction with the THO/TREX complex; key residues in RRM3 essential for THO interaction were identified and genetic interaction with Tho2 was confirmed. NMR structure determination, RNA binding assays, mutagenesis, yeast genetic epistasis (double deletion synthetic phenotype) Nucleic acids research High 26602689
2021 Yeast Gbp2 localizes to cytoplasmic stress granules upon heat shock and oxidative stress, directly binds translation initiation factor eIF4G1 via its RGG motif (mapped to a region overlapping with another repressor Sbp1), and acts as a translation repressor: tethering Gbp2 to a reporter mRNA reduces its translation in vivo, and Gbp2 directly represses translation in vitro in an RGG-motif-dependent manner. Fluorescence imaging, pulldown assay, polysome fractionation, in vivo tethering assay, in vitro translation assay, RGG-motif deletion mutant RNA biology High 33910495
2021 Yeast Gbp2 (and Hrb1) continue quality control on exported transcripts in the cytoplasm: they support nonsense-mediated decay (NMD) by inhibiting translation and recruiting cytoplasmic degradation factors, thereby linking nuclear and cytoplasmic mRNA quality control. Genetic deletion with NMD reporter assays, functional epistasis analysis International journal of molecular sciences Medium 34681934
2023 Human GBP2, like GBP1, directly binds and aggregates 'free' LPS through protein polymerization; supplementation of recombinant polymerized GBP2 to an in vitro reaction is sufficient to enhance LPS-induced caspase-4 activation; GBP2 overexpression can restore gram-negative-induced pyroptosis in GBP1-knockout cells without binding to the bacterial surface, establishing that LPS aggregation (not bacterial surface binding) is sufficient for non-canonical inflammasome activation. In vitro caspase-4 activation assay with recombinant protein, GBP1-KO cell complementation, LPS aggregation assay, protein polymerization assay Proceedings of the National Academy of Sciences of the United States of America High 37023136
2016 The Toxoplasma gondii rhoptry pseudokinase ROP54 modulates host GBP2 loading onto the parasitophorous vacuole membrane; parasites lacking ROP54 show substantially increased GBP2 (but not IRGb6) loading onto the vacuole, indicating ROP54 specifically counteracts GBP2-mediated innate immune defense. Genetic deletion of ROP54 in T. gondii type II strain, immunofluorescence quantification of GBP2 loading, in vivo virulence assay, macrophage clearance assay mSphere Medium 27303719
2020 In glioblastoma cells, GBP2 promotes cell migration and invasion via a GBP2/Stat3/fibronectin (FN1) signaling cascade: GBP2 overexpression induces FN1 at mRNA and protein levels, Stat3 pathway inhibition prevents GBP2-promoted FN1 induction and invasion, and GBP2 promotes tumor growth and invasion in mouse xenograft models. RNAi knockdown and overexpression, in vitro migration/invasion assays, Stat3 inhibitor, in vivo mouse tumor model Oncogene Medium 32518375
2022 Human GBP2 promotes STAT1 phosphorylation by competing with SHP1 for binding to STAT1 in microsatellite-stable colorectal cancer cells, enhancing antigen processing/presentation and CXCL10/11 expression upon IFN-γ stimulation. Co-immunoprecipitation (GBP2/SHP1/STAT1), GBP2 knockout, western blot for p-STAT1, cytokine measurement Journal for immunotherapy of cancer Medium 35383115
2021 GBP-2 (murine) inhibits migration and invadosome formation in breast cancer cells downstream of Rho GTPase regulation, without affecting proliferation; GBP-2 expression is inversely correlated with aggressiveness/metastasis in 4T1 vs. 67NR murine breast cancer cell lines. GBP-2 expression alteration, migration assays, invadosome formation assay, Rho GTPase activity measurement Cancers Medium 34830789
2018 Murine Gbp1 and Gbp2 are ubiquitinated independently of Toxoplasma gondii infection, as identified by mass spectrometry detection of di-glycine ubiquitin remnants on both proteins in IFNγ-stimulated MEFs. Mass spectrometry-based ubiquitinomics (di-glycine remnant profiling) in MEFs BMC research notes Medium 29510761
2025 In Parkinson's disease models, GBP2 undergoes geranylgeranylation (a prenylation modification) driving its accumulation at mitochondria, where it directly binds the mitophagy receptor NIX via its large GTPase domain and promotes NIX ubiquitin-proteasomal degradation, thereby suppressing NIX-mediated mitophagy and causing dopaminergic neuron loss; pharmacological inhibition of geranylgeranylation with GGTI298 attenuates MPTP-induced neurotoxicity. Co-immunoprecipitation (GBP2–NIX), GBP2 knockdown in vivo and in vitro, mitophagy assays, proteasome inhibitor rescue, NIX KD epistasis, GGTI298 pharmacological inhibition, MPTP mouse model Redox biology High 41570768
2025 GBP2 undergoes phase separation through an intrinsically disordered region upon IFN-γ stimulation, forming condensates that sequester SHP1 and sustain STAT1 activation; this enhances STAT1-driven suppression of SLC7A11, sensitizing melanoma tumor cells to ferroptosis; disrupting GBP2 phase separation impairs ferroptosis and tumor control by T cells. Phase separation assay, intrinsically disordered region mutagenesis, co-immunoprecipitation (GBP2–SHP1), western blot for p-STAT1/SLC7A11, HMGB1 release measurement, in vivo tumor growth assay Nature communications High 41444224
2025 EV-packaged GBP2 from macrophages directly binds OTUD5 (a deubiquitinase) and promotes GPX4 ubiquitination and degradation in pulmonary vascular endothelial cells, thereby driving ferroptosis and vascular barrier disruption in sepsis-associated lung injury; the small molecule Plantainoside D inhibits GBP2–OTUD5 interaction and reduces GPX4 ubiquitination. RNA interference, Co-IP (GBP2–OTUD5), AAV transfection, endothelial-specific Gpx4-KO mice, cellular thermal shift assay, molecular docking/dynamics, ubiquitination assay Redox biology High 40156957
2023 GBP2 promotes M1 macrophage polarization by activating the Notch1 signaling pathway in the context of diabetic nephropathy. GBP2 knockdown/overexpression in macrophages, western blot for Notch1 pathway markers, cytokine measurement Frontiers in immunology Low 37622120
2024 GBP2 directly interacts with kinesin family member KIF22 in glioma cells and regulates EGFR signaling through the KIF22/EGFR axis to promote glioma cell proliferation and migration. Co-immunoprecipitation (GBP2–KIF22), GBP2 knockdown/overexpression, EGFR signaling western blot, in vitro proliferation/migration assays Cell death discovery Low 35436989
2024 GBP2 inhibits pathological retinal angiogenesis by suppressing VEGFA expression and secretion through inhibition of the AKT/mTOR signaling pathway in retinal pigment epithelial cells and OIR mouse retinas. GBP2 silencing/overexpression, western blot for AKT/mTOR/VEGFA, VEGFA ELISA, conditioned medium angiogenesis assay with HUVECs, OIR mouse model Microvascular research Low 38636926
2025 In silicosis, GBP2 in macrophages activates the c-Jun pathway to promote M2 macrophage polarization and inflammatory factor secretion; in epithelial cells, GBP2 promotes epithelial-mesenchymal transition (EMT) by upregulating the transcription factor KLF8. Western blot, RT-qPCR, GBP2 knockdown/overexpression, immunofluorescence in THP-1 cells and epithelial cells Xi bao yu fen zi mian yi xue za zhi Low 40620118
2026 ATF4 (master regulator of integrated stress response) promotes GBP2 expression and phosphorylated STAT1 interaction with GBP2, leading to NLRP3 inflammasome activation and tubular epithelial cell pyroptosis in drug-induced AKI; ATF4 suppression disrupts STAT1–GBP2 interaction and attenuates pyroptosis. Single-cell RNA-seq, co-immunoprecipitation (STAT1–GBP2), luciferase reporter, ATF4-specific KO mice, western blotting, pharmacological ATF4 inhibition Journal of the American Society of Nephrology : JASN Medium 41563239
2025 GBP2 promotes podocyte pyroptosis in lupus nephritis via the AIM2 pathway: Gbp2 knockdown reduces GSDMD and AIM2 expression and decreases IL-1β/IL-18 secretion, while Gbp2 overexpression exacerbates these effects; the pyroptosis suppression from Gbp2 knockdown is partially restored by concurrent AIM2 overexpression. siRNA knockdown, overexpression, rescue experiment (AIM2 OE), western blot, cytokine ELISA, in vitro LPS/ATP podocyte pyroptosis model PloS one Medium 41855126
2025 GBP2 suppresses MLV replication by inhibiting furin protease cleavage of the viral envelope glycoprotein SU-TM junction; the sensitivity of MLV Env to GBP2 and furin is determined by the amino acid sequence at the SU-TM cleavage site; substitution of the ecotropic cleavage site sequence with XMRV sequence confers resistance to GBP2, and vice versa. Furin silencing, cleavage site amino acid substitution mutagenesis, infection efficiency assay, western blot for Env cleavage International journal of molecular sciences Medium 39337476
2025 In macrophages, GBP2 promotes M1 polarization and NF-κB pathway activation by recruiting Pin1; nanovaccine-enhanced Gbp2 expression drives TAM reprogramming to M1 phenotype through the Gbp2-Pin1-NFκB pathway. RNA-seq, scRNA-seq, mass spectrometry proteomics, GBP2 targeting in vivo Advanced science Low 39985265
2025 GBP2 promotes non-canonical pyroptosis through the GBP2-caspase-11 axis during Vibrio vulnificus and Salmonella infections; pro-apoptotic proteins Bak and Bax act as positive regulators upstream of Gbp2 upregulation and caspase-11 activation, while anti-apoptotic MCL-1 does not affect this process. Bak-KO and Bax-KO MEFs, caspase-11 activation assay, LDH release, GBP2 western blot Journal of microbiology Medium 41025249

Source papers

Stage 0 corpus · 58 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 99 17293456
2014 Quality control of spliced mRNAs requires the shuttling SR proteins Gbp2 and Hrb1. Nature communications 85 24452287
2020 GBP2 enhances glioblastoma invasion through Stat3/fibronectin pathway. Oncogene 75 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
2019 TCR Affinity Biases Th Cell Differentiation by Regulating CD25, Eef1e1, and Gbp2. Journal of immunology (Baltimore, Md. : 1950) 56 30858199
2022 Subtyping of microsatellite stability colorectal cancer reveals guanylate binding protein 2 (GBP2) as a potential immunotherapeutic target. Journal for immunotherapy of cancer 55 35383115
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
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 51 37023136
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 30 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
2017 Up-regulation of GBP2 is Associated with Neuronal Apoptosis in Rat Brain Cortex Following Traumatic Brain Injury. Neurochemical research 24 28239766
2022 GBP2 facilitates the progression of glioma via regulation of KIF22/EGFR signaling. Cell death discovery 23 35436989
2016 The Rhoptry Pseudokinase ROP54 Modulates Toxoplasma gondii Virulence and Host GBP2 Loading. mSphere 23 27303719
2018 Associations of GBP2 gene copy number variations with growth traits and transcriptional expression in Chinese cattle. Gene 21 29325733
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
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 18 36609599
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
2025 Extracellular vesicle-packaged GBP2 from macrophages aggravates sepsis-induced acute lung injury by promoting ferroptosis in pulmonary vascular endothelial cells. Redox biology 16 40156957
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
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
2022 Plasmodium falciparum GBP2 Is a Telomere-Associated Protein That Binds to G-Quadruplex DNA and RNA. Frontiers in cellular and infection microbiology 12 35273922
2015 The genes Scgb1a1, Lpo and Gbp2 characteristically expressed in peri-implant epithelium of rats. Clinical oral implants research 12 25864924
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
2025 CpG-Based Nanovaccines Enhance Ovarian Cancer Immune Response by Gbp2-Mediated Remodeling of Tumor-Associated Macrophages. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 8 39985265
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
2018 Murine Gbp1 and Gbp2 are ubiquitinated independent of Toxoplasma gondii infection. BMC research notes 4 29510761
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
2024 CENPA facilitates glioma stem cell stemness and suppress ferroptosis to accelerate glioblastoma multiforme progression by promoting GBP2 transcription. Pathology, research and practice 3 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 3 39337460
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 1 40155864
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 Integrated Stress Response and Drug-Induced Acute Kidney Injury: Involvement of Activating ATF4-STAT1-GBP2 Signaling. Journal of the American Society of Nephrology : JASN 0 41563239
2026 Upregulated GBP2 exacerbates Parkinson's disease pathogenesis by impairing NIX-dependent mitophagy. Redox biology 0 41570768
2026 GBP2 promotes podocyte pyroptosis and contributes to the pathogenesis of pediatric lupus nephritis. PloS one 0 41855126
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 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 0 40697643
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