Affinage

G3BP2

Ras GTPase-activating protein-binding protein 2 · UniProt Q9UN86

Length
482 aa
Mass
54.1 kDa
Annotated
2026-06-09
58 papers in source corpus 36 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

G3BP2 is a multifunctional RNA-binding scaffold protein that nucleates stress granule (SG) assembly and couples cytoplasmic mRNA fate and protein sequestration to mechanical, hormonal, and stress signals (PMID:23279204, PMID:25893917). Through its NTF2-like domain it forms homo- and hetero-multimers with G3BP1 and engages FGDF-motif partners, with the domain crystallizing as a homodimer that binds FGDF peptides via a hydrophobic surface (PMID:26410532); both G3BPs are required for efficient SG formation, and G3BP2 overexpression alone induces SGs without stress (PMID:23279204). As a cytoplasmic sequestering platform, G3BP2 retains TWIST1 under low matrix stiffness to restrain EMT and metastasis (PMID:25893917), and drives RanBP2/TRIM25-dependent SUMOylation and nuclear export of p53 to suppress its tumor-suppressor activity downstream of androgen receptor induction (PMID:28692047, PMID:29379164). G3BP2 additionally controls the stability and translation of specific transcripts—stabilizing SART3, HDGF, and PD-L1 mRNAs while degrading c-Myc mRNA—to influence stemness, migration, and immune evasion (PMID:28096337, PMID:34782720, PMID:33525064, PMID:33476486). Its activity is tuned by a layered code of post-translational modifications: phosphorylation at Thr226/Thr227 by RIOK1 and MAP4K4, arginine methylation at R468 by PRMT5 (promoting USP7-mediated deubiquitination and stabilization), and K76 acetylation by p300 reversed by HDAC6 (enhancing PABPC1 and PD-L1 mRNA binding) (PMID:35589951, PMID:38639383, PMID:36878903, PMID:41906099). In antiviral immunity G3BP2 supports SG-based defenses and is a target for viral antagonism: it associates with alphavirus replication proteins, is proteolytically cleaved by foot-and-mouth disease virus Lpro to disable SGs, and redundantly with G3BP1 restricts SARS-CoV-2 whose N protein disrupts the G3BP–SG axis (PMID:20392851, PMID:25653451, PMID:30404792, PMID:40733530). G3BP2 also directly binds Tau, masking its microtubule-binding region to inhibit aggregation, and its loss elevates Tau pathology in human neurons (PMID:37385246).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 2010 Medium

    Established the first physical link between G3BP2 and viral RNA replication machinery, raising the question of whether host SG proteins are co-opted or antiviral during alphavirus infection.

    Evidence Affinity purification/MS of FLAG-tagged Sindbis virus nsP4 with functional depletion in infected cells

    PMID:20392851

    Open questions at the time
    • Interaction identified by MS without direct binary binding validation
    • Whether G3BP2 promotes or limits replication not cleanly resolved here
  2. 2012 High

    Defined G3BP2 as a core SG scaffold by showing it multimerizes with G3BP1 and is itself sufficient to induce SGs, identifying the molecular building block of granule assembly.

    Evidence Reciprocal Co-IP, single/double siRNA knockdown, overexpression, and SG immunofluorescence counting

    PMID:23279204

    Open questions at the time
    • Did not resolve the structural basis of multimerization
    • RNA targets within SGs not defined
  3. 2012 High

    Connected G3BP2 to signal-dependent regulation, identifying PKCα as a direct binding kinase and arginine methylation as a Wnt-responsive switch, indicating its activity is post-translationally controlled.

    Evidence RNase-resistant Co-IP, recombinant in vitro kinase assay, methyltransferase inhibition and methylation-deficient mutants with LRP6 phosphorylation readout

    PMID:22357953 PMID:22536444

    Open questions at the time
    • PKCα phosphorylation sites on G3BP2 not mapped
    • Functional consequence of PKCα phosphorylation on SG dynamics unresolved
  4. 2014 High

    Showed G3BP2 acts in translational control of antiviral ISG mRNAs and is a target of flaviviral subversion, framing it as both a host defense factor and a viral target.

    Evidence siRNA knockdown with polysome/translation assays and sfRNA RNA pulldown demonstrating direct binding

    PMID:24992036

    Open questions at the time
    • mRNA-binding determinants on G3BP2 not mapped
    • Mechanism by which sfRNA sponging blocks translation not detailed
  5. 2015 High

    Defined G3BP2 as a mechanotransducer that sequesters TWIST1 in the cytoplasm, answering how matrix stiffness gates EMT and metastasis.

    Evidence Co-IP, knockdown, live-cell imaging, and in vivo tumor models

    PMID:25893917

    Open questions at the time
    • Molecular sensor of stiffness that releases TWIST1 not identified
    • Binding interface on G3BP2 for TWIST1 not mapped
  6. 2015 High

    Resolved the structural basis of partner engagement by crystallizing the G3BP2 NTF2-like domain bound to an FGDF peptide, establishing the homodimeric module that underlies SG and viral protein interactions.

    Evidence X-ray crystallography of NTF2-like/FGDF complex at 2.75 Å

    PMID:26410532

    Open questions at the time
    • Full-length protein architecture and RNA-binding domain not structurally defined
    • How dimerization translates to granule condensation not addressed
  7. 2017 High

    Placed G3BP2 in an androgen-receptor-driven oncogenic axis that exports p53, explaining how its overexpression inactivates a tumor suppressor in prostate cancer.

    Evidence ChIP for AR induction, Co-IP for G3BP2-RanBP2, fractionation/IF for p53 localization, xenografts

    PMID:28692047

    Open questions at the time
    • Direct G3BP2 contribution to SUMO-ligase activity not biochemically defined
    • Generality beyond prostate cancer untested at this stage
  8. 2017 Medium

    Extended the mRNA-stabilizing role of G3BP2 to cancer stemness by linking it to SART3 mRNA and pluripotency factors.

    Evidence Chemical-probe (C108) target ID, mRNA stability assays, knockdown/overexpression with TIC readouts

    PMID:28096337

    Open questions at the time
    • Direct G3BP2-SART3 mRNA binding sites not mapped
    • Single lab
  9. 2018 Medium

    Identified TRIM25 and USP10 as regulators of the G3BP2-p53 export axis and of G3BP2 stability, revealing how complex membership and deubiquitination sustain its oncogenic function.

    Evidence Co-IP, ubiquitination assays, knockdown with p53 localization and growth phenotypes, xenografts

    PMID:29378906 PMID:29379164

    Open questions at the time
    • E3 ligase opposing USP10 not identified
    • Reciprocal validation of complexes limited to single labs
  10. 2019 High

    Demonstrated that viral proteases directly disable G3BP2 to dismantle SG defenses, distinguishing scaffold cleavage from upstream stress kinase signaling.

    Evidence Recombinant chimeric virus, immunoblot for cleavage, SG assays, PKR/eIF2α phosphorylation controls, replicated in a second virus

    PMID:30404792

    Open questions at the time
    • Precise cleavage site within G3BP2 not specified here
    • Consequences for non-SG functions of G3BP2 untested
  11. 2019 Medium

    Showed α-parvin gates the G3BP2-TWIST1 interaction and TWIST1 degradation, refining how upstream adhesion-linked factors control the mechanosensitive sequestration circuit.

    Evidence Co-IP of both complexes, ubiquitination assay, domain-mutant rescue, knockdown, in vivo tumor models

    PMID:30804457

    Open questions at the time
    • Mechanism by which α-parvin displaces TWIST1 not structurally defined
    • Single lab
  12. 2020 Medium

    Linked G3BP2 to inflammatory signaling by controlling IκBα localization and NF-κB activity in vascular and cardiac contexts, broadening its role beyond cancer and stress granules.

    Evidence Co-IP (G3BP2-IκBα), knockdown/overexpression, NF-κB reporters, fractionation, and ApoE-/- mouse models

    PMID:28816235 PMID:32919187

    Open questions at the time
    • Whether G3BP2-IκBα binding directly alters IκBα degradation unresolved
    • Tissue specificity of the effect not delineated
  13. 2021 Medium

    Expanded the G3BP2 mRNA regulon to HDGF, PD-L1, and c-Myc, establishing it as a sequence-selective controller of transcript stability driving migration, immune evasion, and proliferation.

    Evidence RIP/RNA pulldown, mRNA stability and luciferase reporter assays, knockdown with rescue, in vivo tumor immunology

    PMID:33476486 PMID:33525064 PMID:34782720

    Open questions at the time
    • Binding motif distinguishing stabilized vs degraded targets unknown
    • Each target characterized in a single tumor context
  14. 2021 Medium

    Identified MG53/TRIM72 as a factor that drives nuclear translocation of G3BP2 to block SG formation, positioning G3BP2 as an essential downstream effector of an anti-proliferative pathway.

    Evidence Co-IP with TRIM domain mapping, shRNA knockdown, live imaging, allograft/xenograft models

    PMID:34521423

    Open questions at the time
    • Mechanism of forced nuclear import not defined
    • Single lab
  15. 2022 High

    Established phosphorylation by RIOK1 at Thr226 as an activating modification that amplifies G3BP2-driven p53 degradation and radioresistance, opening the post-translational regulatory layer.

    Evidence Co-IP, in vitro kinase assay with site ID, ubiquitination assay, inhibition, in vivo tumor models

    PMID:35589951

    Open questions at the time
    • How phosphorylation mechanistically enhances p53 degradation not structurally resolved
    • Single tumor model
  16. 2023 Medium

    Revealed a PRMT5/USP7 arginine-methylation/deubiquitination axis stabilizing G3BP2 and a metabolic output via ACLY, integrating PTM control with lipogenesis and tumorigenesis.

    Evidence Co-IP, methylation site ID (R468me2), deubiquitination assays, PRMT5 inhibition, ACLY activity, in vivo models

    PMID:36878903

    Open questions at the time
    • How stabilized G3BP2 activates ACLY mechanistically unclear
    • Single lab
  17. 2023 High

    Showed G3BP2 directly binds Tau and masks its microtubule-binding region to inhibit aggregation, defining a protective function in tauopathy.

    Evidence Co-IP, in vitro aggregation assays, KO in human neurons and brain organoids, post-mortem tissue analysis

    PMID:37385246

    Open questions at the time
    • Structural basis of MTBR masking not resolved
    • Whether SG assembly is required for the protective effect unclear
  18. 2023 Medium

    Connected G3BP2 to mTORC1 regulation and stress-dependent mRNA-translation reprogramming, showing it recruits TSC2 via an HDAC6 complex and partitions transcripts in SGs.

    Evidence Co-IP of HDAC6-G3BP2-TSC2 complex, mTORC1 activity and deacetylation assays, RIP, SG isolation

    PMID:36823378 PMID:39289547

    Open questions at the time
    • Direct vs scaffolding role in TSC2 recruitment not separated
    • Selectivity of mRNA partitioning into SGs not generalized
  19. 2024 Medium

    Identified MAP4K4 phosphorylation at Thr227 downstream of dipeptide import as a metabolic-stimulus-driven activating modification promoting metastasis.

    Evidence Co-IP of PEPT1-MAP4K4-G3BP2 axis, phospho-site ID, knockdown/overexpression, in vivo metastasis models

    PMID:38639383

    Open questions at the time
    • Relationship between Thr226 and Thr227 phosphorylation events not reconciled
    • Single lab
  20. 2024 Medium

    Documented a nuclear PSF-G3BP2 complex stabilizing pre-mRNAs to support neuronal viability, extending G3BP2 function into the nucleus and neurodegeneration.

    Evidence Co-IP of nuclear complex, RNA-seq, qRT-PCR stability, aged mouse and human AD brain tissue

    PMID:39155453

    Open questions at the time
    • Direct vs indirect nuclear RNA targets not defined
    • Causal link between reduced G3BP2 and AD pathology not established
  21. 2025 Medium

    Resolved the redundancy and antiviral logic of G3BPs against SARS-CoV-2 and showed the N protein hijacks the G3BP2-TRIM25 interface to suppress interferon, clarifying virus-host competition at the SG scaffold.

    Evidence CRISPR double KO with viral replication assays, interaction-residue mapping, IFN production assays in infected cells

    PMID:36560452 PMID:40733530

    Open questions at the time
    • Quantitative split of G3BP1 vs G3BP2 contributions not resolved
    • Whether SG disruption alone explains the IFN phenotype unclear
  22. 2025 Medium

    Implicated G3BP2 in ubiquitin/lysosome-mediated turnover of signaling proteins (STAT1, eIF3A), with lncRNAs competing for G3BP2 to tune antiviral and stress responses.

    Evidence Co-IP, ubiquitination assays, MS complex ID, knockdown epistasis, ISG/lysosomal inhibitor experiments, in vivo infection

    PMID:40188129 PMID:40626722

    Open questions at the time
    • Whether G3BP2 acts as adaptor or directly recruits ligases unresolved
    • These degradation roles each rest on single studies
  23. 2026 Medium

    Defined acetylation at K76 (p300 writer, HDAC6 eraser) as a modification that boosts PABPC1 and PD-L1 mRNA binding, completing a multi-PTM control map governing G3BP2 mRNA targeting and immune evasion.

    Evidence Co-IP, RIP, acetylation site mutagenesis, writer/eraser identification, mRNA stability, immunocompetent mouse models

    PMID:41906099

    Open questions at the time
    • Interplay between K76 acetylation and other PTMs not mapped
    • Single tumor type
  24. 2026 High

    Provided structural insight into G3BP2 degradability by showing cereblon molecular glues engage an unconventional LON-domain site exploiting a native PPI hotspot, establishing G3BP2 as a tractable degrader neosubstrate.

    Evidence Ternary complex structural analysis, biochemical ubiquitination assays, proteomics

    PMID:41559416

    Open questions at the time
    • Identity of the endogenous partner mimicked by CRBN not confirmed
    • Functional consequence of induced G3BP2 degradation in cells not characterized here

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the layered PTM code, partner sequestration, and selective mRNA stabilization/degradation are integrated to determine when G3BP2 protects (Tau, antiviral) versus promotes disease (oncogenic p53 export, immune evasion) remains unresolved.
  • No unified model linking PTM state to specific mRNA target choice
  • Structural basis for full-length G3BP2 RNA recognition undefined
  • Determinants of nuclear vs cytoplasmic vs SG localization not mechanistically dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 7 GO:0060090 molecular adaptor activity 4 GO:0140313 molecular sequestering activity 3 GO:0005198 structural molecule activity 2 GO:0045182 translation regulator activity 2
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 2
Pathway
R-HSA-168256 Immune System 5 R-HSA-392499 Metabolism of proteins 5 R-HSA-8953854 Metabolism of RNA 5 R-HSA-162582 Signal Transduction 4 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-1643685 Disease 3
Partners
G3BP1HDAC6PABPC1RANBP2TRIM25TSC2TWIST1USP10
Complex memberships
G3BP1-G3BP2 multimerstress granule

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 G3BP2 sequesters TWIST1 in the cytoplasm under low matrix stiffness; increasing matrix stiffness releases TWIST1 from G3BP2, allowing its nuclear translocation to drive EMT. Loss of G3BP2 leads to constitutive TWIST1 nuclear localization, promoting invasion and metastasis. Co-immunoprecipitation, loss-of-function (knockdown), live-cell imaging, in vivo tumor models Nature Cell Biology High 25893917
2012 G3BP2 forms homo-multimers and hetero-multimers with G3BP1, and both proteins are required for stress granule (SG) formation; single knockdown of either partially reduces SGs, while double knockdown significantly reduces SG-positive cells. Overexpression of G3BP2 alone is sufficient to induce SG formation without stress stimuli. siRNA knockdown, co-immunoprecipitation, overexpression, immunofluorescence (SG counting) Genes to Cells High 23279204
2014 G3BP2 (together with G3BP1 and CAPRIN1) is required for efficient translation of interferon-stimulated gene (ISG) mRNAs including PKR and IFITM2; dengue virus sfRNA acts as a molecular sponge that binds G3BP2 and inhibits this translational regulatory activity. siRNA knockdown, polysome/translation assays, RNA pulldown (sfRNA-protein interaction), ISG protein accumulation assays PLoS Pathogens High 24992036
2015 CHIKV nsP3 interacts with G3BP2 (and G3BP1) in cytoplasmic foci that differ from canonical SGs. Simultaneous depletion of G3BP1 and G3BP2 reduces viral RNA levels, CHIKV protein expression, and progeny titers, suggesting G3BPs facilitate the switch from viral genome translation to amplification early in infection. Co-immunoprecipitation (nsP3-G3BP2 interaction), siRNA double knockdown, viral RNA quantification, viral titer assays, immunofluorescence co-localization Journal of Virology High 25653451
2010 G3BP2 (and G3BP1) physically associate with Sindbis virus nsP4 (RNA-dependent RNA polymerase) throughout infection and play an overlapping role in limiting SINV replication events. Affinity purification of FLAG-tagged nsP4 complexes followed by proteomic (MS) analysis, functional depletion assays Journal of Virology Medium 20392851
2017 Androgen receptor (AR) transcriptionally induces G3BP2 expression; elevated G3BP2 interacts with the SUMO-E3 ligase RanBP2 to promote SUMO-mediated cytoplasmic export of p53, thereby inhibiting p53 tumor suppressor activity and driving prostate cancer progression. ChIP, siRNA knockdown, subcellular fractionation/immunofluorescence for p53 localization, in vivo xenograft models Oncogene High 28692047
2018 TRIM25 interacts with G3BP2 protein complex and is important for G3BP2/RanBP2-mediated p53 nuclear export and sumoylation; TRIM25 knockdown restores nuclear p53 and activates downstream p53 signaling for cell cycle arrest and apoptosis. Co-immunoprecipitation, siRNA knockdown, cell cycle/apoptosis assays, in vivo xenograft Oncogene Medium 29379164
2018 USP10 physically interacts with G3BP2 in stress granules and maintains G3BP2 protein stability by reducing its polyubiquitylation (deubiquitination). USP10 knockdown reduces G3BP2 levels, relieves G3BP2-dependent p53 nuclear export suppression, and decreases cell growth. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, protein stability assays Molecular Cancer Research Medium 29378906
2017 G3BP2 stabilizes SART3 mRNA, leading to increased expression of pluripotency transcription factors Oct-4 and Nanog, thereby regulating breast tumor-initiating cell (TIC) activity. Chemical screening identifying G3BP2 as a binding partner of compound C108, mRNA stability assays, knockdown/overexpression with TIC phenotypic readouts PNAS Medium 28096337
2012 PKCα directly interacts with G3BP2 via its regulatory domain (binding to the C-terminal RNA-binding domain of G3BP2) in an RNA-independent manner; PKCα can phosphorylate G3BP2 in vitro. Both proteins co-localize in stress granules during cellular stress, and PKCα knockdown suppresses heat shock-induced SG assembly. Co-immunoprecipitation with/without RNase treatment, recombinant protein interaction assay, in vitro kinase assay, siRNA knockdown, immunofluorescence PLoS One High 22536444
2012 G3BP2 is methylated on arginine residues in response to Wnt3a signaling; this methylation acts as a switch regulating Wnt3a-stimulated LRP6 phosphorylation and canonical Wnt-β-catenin signaling. G3BP2 is a dishevelled-associated protein, and its knockdown or methylation-deficient mutants attenuate LRP6 phosphorylation. Co-immunoprecipitation (G3BP2-dishevelled), methyltransferase inhibitor treatment, methylation-deficient mutant expression, siRNA knockdown, LRP6 phosphorylation assay Journal of Cell Science Medium 22357953
2015 Crystal structure of the G3BP2 NTF2-like domain in complex with an FGDF-motif peptide at 2.75 Å resolution; the domain forms a homodimer structurally similar to G3BP1 and Rasputin NTF2-like domains. The FGDF peptide binds via hydrophobic interactions to a symmetry-related molecule, revealing a binding mode distinct from that predicted by molecular modeling. X-ray crystallography Biochemical and Biophysical Research Communications High 26410532
2017 G3BP2 directly interacts with IκBα and promotes nuclear accumulation of NF-κB p65 subunit, increasing NF-κB transcriptional activity. G3BP2 overexpression induces cardiomyocyte hypertrophy that is suppressed by NF-κB inhibition or p65 knockdown, placing G3BP2 upstream of NF-κB in hypertrophic signaling. Co-immunoprecipitation (G3BP2-IκBα), overexpression/knockdown in neonatal rat cardiomyocytes, NF-κB luciferase reporter assay, immunofluorescence for p65 localization Acta Pharmacologica Sinica Medium 28816235
2019 Foot-and-mouth disease virus leader protease (Lpro) cleaves G3BP2 (and G3BP1) but not TIA-1, thereby suppressing stress granule formation. This cleavage activity is conserved in equine rhinitis A virus Lpro. Lpro does not affect PKR or eIF2α phosphorylation, indicating it acts on SG scaffolding proteins directly rather than upstream signaling. Recombinant chimeric virus system, immunoblot for G3BP2 cleavage, SG formation assay, PKR/eIF2α phosphorylation assay Journal of Virology High 30404792
2021 MG53 (TRIM72) physically interacts with G3BP2 via its TRIM domain and induces nuclear translocation of G3BP2, blocking stress granule formation. Knockdown of MG53 enhances NSCLC cell proliferation/migration; the anti-proliferative effect of recombinant MG53 is abolished by G3BP2 knockout, placing G3BP2 as an essential downstream effector. Co-immunoprecipitation (MG53-G3BP2 via TRIM domain), shRNA knockdown, live cell imaging, in vivo allograft/xenograft mouse models Molecular Cancer Medium 34521423
2022 RIOK1 kinase directly interacts with G3BP2 and phosphorylates it at Thr226; this phosphorylation increases G3BP2 activity and facilitates MDM2-mediated ubiquitination and degradation of p53, thereby suppressing p53 signaling and promoting radioresistance in colorectal cancer. Co-immunoprecipitation, in vitro kinase assay with phospho-site identification, ubiquitination assay, siRNA/pharmacological inhibition, in vivo tumor models Oncogene High 35589951
2021 G3BP2 upregulates PD-L1 expression under stress conditions by stabilizing PD-L1 mRNA; genetic repression of G3BP2 or treatment with compound C108 (which binds G3BP2) leads to enhanced PD-L1 mRNA degradation, decreased PD-L1 protein, and increased CD8+ T cell infiltration in tumors. G3BP2 knockdown/C108 treatment, mRNA stability assays, in vivo tumor immunology (CD8+ T cell analysis, survival) Molecular Oncology Medium 33525064
2023 G3BP2 directly interacts with Tau protein and masks the microtubule-binding region (MTBR) of Tau, thereby inhibiting Tau aggregation. The G3BP2-Tau interaction is dramatically increased in multiple human tauopathies, and loss of G3BP2 in human neurons and brain organoids significantly elevates Tau pathology. Co-immunoprecipitation, in vitro aggregation assays, G3BP2 knockout in human neurons and brain organoids, post-mortem human brain tissue analysis Neuron High 37385246
2021 G3BP2 regulates HDGF mRNA stability by directly binding to HDGF mRNA transcript; loss of G3BP2 reduces HDGF expression and suppresses ESCC cell migration, and HDGF re-expression rescues the G3BP2 depletion phenotype. RNA-seq, RNA immunoprecipitation (RIP), siRNA knockdown, rescue experiment with HDGF overexpression Oncogene Medium 34782720
2021 G3BP2 inhibits BAALC-AS1-mediated stabilization of c-Myc mRNA: BAALC-AS1 directly interacts with G3BP2 and blocks G3BP2-mediated degradation of c-Myc mRNA 3'-UTR, leading to c-Myc accumulation and ESCC cell proliferation. RNA immunoprecipitation, RNA pulldown assay, luciferase reporter (c-Myc 3'-UTR), siRNA knockdown Cancer Communications Medium 33476486
2023 PRMT5 methylates G3BP2 at Arg468 (R468me2), which enhances its binding to the deubiquitinase USP7; USP7 then deubiquitinates and stabilizes G3BP2. Stabilized G3BP2 activates ACLY to stimulate de novo lipogenesis and tumorigenesis in head and neck squamous carcinoma. Co-immunoprecipitation, methylation site identification (R468me2), deubiquitination assays, PRMT5 inhibitor/KD experiments, ACLY activity assays, in vivo tumor models Cell Death & Disease Medium 36878903
2022 SARS-CoV-2 nucleocapsid (N) protein promotes the interaction between G3BP2 and TRIM25, forming a TRIM25-G3BP2-N protein interactome. This enhanced G3BP2-TRIM25 binding interferes with RIG-I-like receptor signaling, suppressing type I interferon production. Co-immunoprecipitation in SARS-CoV-2-infected cells, proteomic interactome analysis, IFN production assay Vaccines Medium 36560452
2025 G3BP1 and G3BP2 redundantly suppress SARS-CoV-2 replication; ablation of both G3BP1 and G3BP2 enhances SARS-CoV-2 replication. The interaction between G3BP1/G3BP2 and the viral N protein disrupts stress granule formation, and specific residues required for this interaction were confirmed. CRISPR knockout of G3BP1 and G3BP2, viral replication assay, Co-IP/interaction mapping for N protein binding residues, SG formation assay Viruses Medium 40733530
2024 MAP4K4 phosphorylates G3BP2 at Thr227, triggered by cellular dipeptides imported via PEPT1; this phosphorylation enhances G3BP2 activity and promotes HCC cell metastasis. Co-immunoprecipitation (PEPT1-MAP4K4-G3BP2 axis), phosphorylation site identification (Thr227), siRNA/overexpression experiments, in vivo metastasis models Advanced Science Medium 38639383
2023 G3BP2 binds PDIA3 mRNA and recruits it into stress granules, increasing PDIA3 mRNA stability but attenuating its translation, which promotes DKC1 expression. DKC1 in turn binds hENT mRNA and inhibits its expression, enhancing gemcitabine resistance in pancreatic ductal adenocarcinoma. RNA immunoprecipitation, stress granule isolation, gene expression analysis upon G3BP2 KD/OE, rescue experiments Acta Pharmacologica Sinica Medium 39289547
2024 PSF interacts with G3BP2 in the nucleus and in stress granules; their cooperative action stabilizes target pre-mRNA transcripts and sustains neuronal cell viability. Both PSF and G3BP2 levels are decreased in aged and Alzheimer's disease brains. Co-immunoprecipitation (PSF-G3BP2 nuclear interaction), RNA-seq, qRT-PCR for mRNA stability, aged mouse brain and human AD brain tissue analysis Aging Cell Medium 39155453
2019 α-Parvin interacts with G3BP2; when α-parvin is present, it prevents G3BP2 interaction with TWIST1. Knockdown of α-parvin promotes G3BP2-TWIST1 interaction, increases ubiquitination and proteasome-dependent degradation of TWIST1, reducing TWIST1 levels and downstream signaling. G3BP2 depletion reverses the suppression of TWIST1 caused by α-parvin loss. Co-immunoprecipitation (α-parvin-G3BP2 and G3BP2-TWIST1), ubiquitination assay, domain mutant rescue, siRNA knockdown, in vivo tumor models Oncogene Medium 30804457
2020 G3BP2 regulates IκBα localization in endothelial cells; knockdown of G3BP2 reduces ox-LDL-induced inflammation via controlling IκBα localization, and G3bp2 knockout in ApoE-/- mice decreases atherosclerotic lesions with reduced pro-inflammatory cytokines. siRNA knockdown, Co-IP (G3BP2-IκBα), subcellular fractionation for IκBα localization, in vivo ApoE-/- mouse model Atherosclerosis Medium 32919187
2021 Loss of G3BP2 in endothelial cells exposed to oscillatory shear stress increases YAP nucleocytoplasmic shuttling and phosphorylation, thereby diminishing OSS-induced inflammation. G3bp2 knockout in ApoE-/- mice decreases atherosclerotic lesions by protecting endothelial barrier function and reducing monocyte adhesion. siRNA/shRNA knockdown, partial ligation mouse model, RNA-seq, YAP localization/phosphorylation assays, in vivo G3bp2 Apoe double-knockout Genes & Diseases Medium 36157502
2023 G3BP2 recruits lysosomal TSC2 to suppress mTORC1 under low-lactate stress; HDAC6 deacetylates TSC2 to sustain its stability and associates with G3BP2 to facilitate TSC2 recruitment, forming an HDAC6-G3BP2 complex that drives mTORC1 inhibition. HDAC6's microtubule retrograde transport activity promotes perinuclear mTOR distribution under stress. Co-immunoprecipitation (G3BP2-HDAC6-TSC2 complex), mTORC1 activity assays, HDAC6 deacetylation assay, live cell imaging of mTOR distribution Oncogene Medium 36823378
2026 Cereblon (CRBN) can be directed by molecular glue degraders (MGDs) to ubiquitinate and degrade G3BP2 as a neosubstrate. The ternary complex structure reveals G3BP2 engages an unconventional binding site on the CRBN LON domain (not the canonical CULT domain G-loop), and CRBN mimics an endogenous binding partner of G3BP2 by exploiting a pre-existing PPI hotspot on G3BP2. Crystal/structural analysis of ternary complex, biochemical ubiquitination assay, proteomics Nature Structural & Molecular Biology High 41559416
2025 G3BPs (G3BP1 and G3BP2) and stress granules are necessary and sufficient to reinforce the integrated stress response translation program: they help prioritize translation of stress-resistant mRNAs enriched in SGs and suppress global cytosolic translation during stress, demonstrated using optogenetic tools and spike-normalized ribosome profiling. Optogenetic SG induction, spike-normalized ribosome profiling, G3BP1/2 double knockout, mRNA enrichment analysis in SGs bioRxiv (preprint)preprint Medium
2025 G3BP2 promotes ubiquitin-mediated degradation of STAT1; a lncRNA (LINC2781) directly binds G3BP2 and prevents this G3BP2-mediated STAT1 degradation through ubiquitination, thereby activating JAK-STAT signaling and antiviral ISG expression. Co-immunoprecipitation (G3BP2-STAT1 and LINC2781-G3BP2), ubiquitination assay, siRNA knockdown, ISG expression assay, in vivo mouse infection model mSphere Medium 40626722
2026 G3BP2 acetylation at lysine 76 (K76), catalyzed by p300 and reversed by HDAC6, enhances G3BP2 binding to PABPC1 and PD-L1 mRNA, increasing PD-L1 mRNA stability and PD-L1 protein expression, thereby promoting immune evasion in colorectal cancer. Co-immunoprecipitation (G3BP2-PABPC1), RNA immunoprecipitation (G3BP2-PD-L1 mRNA), acetylation site mutagenesis, p300/HDAC6 writer-eraser identification, mRNA stability assay, in vivo immunocompetent mouse models Cell Communication and Signaling Medium 41906099
2025 ROBO1 interacts with eIF3A and G3BP2 after irradiation, forming a hetero-complex that triggers lysosome-mediated eIF3A degradation; G3BP2 knockdown abrogates ROBO1's effect on eIF3A instability, placing G3BP2 as an essential component of this degradation complex. Co-immunoprecipitation, mass spectrometry (complex identification), siRNA knockdown epistasis, lysosomal inhibitor experiments Cell Death & Disease Medium 40188129
2025 EPS8L2 increases YBX1 phosphorylation by enhancing YBX1's interaction with S6K1; phosphorylated YBX1 translocates to the nucleus and initiates G3BP2 transcription, activating the MAPK signaling pathway to drive colorectal cancer proliferation and metastasis. Co-immunoprecipitation (EPS8L2-YBX1-S6K1), YBX1 phosphorylation assay, nuclear translocation assay, G3BP2 promoter-reporter, MAPK pathway activation assay, in vivo AOM/DSS mouse model Cell Death & Disease Medium 40783393
2025 G3BP2 suppresses p53 signaling in rheumatoid arthritis fibroblast-like synoviocytes (FLSs) by promoting p53 ubiquitination; G3BP2 silencing or compound C108 treatment reduces p53 ubiquitination, increases nuclear p53 levels, and suppresses RA-FLS migration and invasion. The p53 inhibitor PFT-α reverses the C108 inhibitory effect, confirming epistatic placement. siRNA knockdown, compound C108 treatment, ubiquitination assay for p53, RNA sequencing, p53 inhibitor epistasis, in vivo adjuvant-induced arthritis rat model International Immunopharmacology Medium 41338150

Source papers

Stage 0 corpus · 58 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Matrix stiffness drives epithelial-mesenchymal transition and tumour metastasis through a TWIST1-G3BP2 mechanotransduction pathway. Nature cell biology 750 25893917
2012 Both G3BP1 and G3BP2 contribute to stress granule formation. Genes to cells : devoted to molecular & cellular mechanisms 254 23279204
2014 G3BP1, G3BP2 and CAPRIN1 are required for translation of interferon stimulated mRNAs and are targeted by a dengue virus non-coding RNA. PLoS pathogens 230 24992036
2018 Invasion-related circular RNA circFNDC3B inhibits bladder cancer progression through the miR-1178-3p/G3BP2/SRC/FAK axis. Molecular cancer 140 30458784
2015 Stress granule components G3BP1 and G3BP2 play a proviral role early in Chikungunya virus replication. Journal of virology 136 25653451
2010 Host factors associated with the Sindbis virus RNA-dependent RNA polymerase: role for G3BP1 and G3BP2 in virus replication. Journal of virology 97 20392851
2018 TRIM25 enhances cell growth and cell survival by modulating p53 signals via interaction with G3BP2 in prostate cancer. Oncogene 96 29379164
2019 Foot-and-Mouth Disease Virus Leader Protease Cleaves G3BP1 and G3BP2 and Inhibits Stress Granule Formation. Journal of virology 90 30404792
2018 Association of USP10 with G3BP2 Inhibits p53 Signaling and Contributes to Poor Outcome in Prostate Cancer. Molecular cancer research : MCR 82 29378906
2017 Stress granule-associated protein G3BP2 regulates breast tumor initiation. Proceedings of the National Academy of Sciences of the United States of America 82 28096337
2017 Androgen induces G3BP2 and SUMO-mediated p53 nuclear export in prostate cancer. Oncogene 66 28692047
2021 MG53 suppresses tumor progression and stress granule formation by modulating G3BP2 activity in non-small cell lung cancer. Molecular cancer 62 34521423
2017 G3BP2 is involved in isoproterenol-induced cardiac hypertrophy through activating the NF-κB signaling pathway. Acta pharmacologica Sinica 46 28816235
2012 PKCα binds G3BP2 and regulates stress granule formation following cellular stress. PloS one 46 22536444
2012 Wnt3a-stimulated LRP6 phosphorylation is dependent upon arginine methylation of G3BP2. Journal of cell science 43 22357953
2015 Crystal structure of the G3BP2 NTF2-like domain in complex with a canonical FGDF motif peptide. Biochemical and biophysical research communications 42 26410532
2023 Chemotherapy-induced exosomal circBACH1 promotes breast cancer resistance and stemness via miR-217/G3BP2 signaling pathway. Breast cancer research : BCR 41 37461019
2022 G3BP2: Structure and function. Pharmacological research 39 36336216
2022 RIOK1 mediates p53 degradation and radioresistance in colorectal cancer through phosphorylation of G3BP2. Oncogene 33 35589951
2021 Repression of the stress granule protein G3BP2 inhibits immune checkpoint molecule PD-L1. Molecular oncology 27 33525064
2022 G3BP2 regulated by the lncRNA LINC01554 facilitates esophageal squamous cell carcinoma metastasis through stabilizing HDGF transcript. Oncogene 25 34782720
2020 FOXD1 Repression Potentiates Radiation Effectiveness by Downregulating G3BP2 Expression and Promoting the Activation of TXNIP-Related Pathways in Oral Cancer. Cancers 23 32967107
2024 Exosomal miRNA-92a derived from cancer-associated fibroblasts promote invasion and metastasis in breast cancer by regulating G3BP2. Cellular signalling 22 38640983
2023 Increased G3BP2-Tau interaction in tauopathies is a natural defense against Tau aggregation. Neuron 22 37385246
2021 BAALC-AS1/G3BP2/c-Myc feedback loop promotes cell proliferation in esophageal squamous cell carcinoma. Cancer communications (London, England) 22 33476486
2019 G3BP1 and G3BP2 regulate translation of interferon-stimulated genes: IFITM1, IFITM2 and IFITM3 in the cancer cell line MCF7. Molecular and cellular biochemistry 22 31172368
2023 HDAC6-G3BP2 promotes lysosomal-TSC2 and suppresses mTORC1 under ETV4 targeting-induced low-lactate stress in non-small cell lung cancer. Oncogene 21 36823378
2021 G3BP2 regulates oscillatory shear stress-induced endothelial dysfunction. Genes & diseases 21 36157502
2020 Downregulation of G3BP2 reduces atherosclerotic lesions in ApoE-/- mice. Atherosclerosis 21 32919187
2023 USP7- and PRMT5-dependent G3BP2 stabilization drives de novo lipogenesis and tumorigenesis of HNSC. Cell death & disease 19 36878903
2019 α-Parvin promotes breast cancer progression and metastasis through interaction with G3BP2 and regulation of TWIST1 signaling. Oncogene 19 30804457
2021 MiR-124-3p Suppresses the Dysfunction of High Glucose-Stimulated Endothelial Cells by Targeting G3BP2. Frontiers in genetics 18 34691148
2017 Correction: G3BP1, G3BP2 and CAPRIN1 Are Required for Translation of Interferon Stimulated mRNAs and Are Targeted by a Dengue Virus Non-coding RNA. PLoS pathogens 16 28350882
2022 EBF1-mediated up-regulation of lncRNA FGD5-AS1 facilitates osteosarcoma progression by regulating miR-124-3p/G3BP2 axis as a ceRNA. Journal of orthopaedic surgery and research 14 35761386
2022 Engagement of the G3BP2-TRIM25 Interaction by Nucleocapsid Protein Suppresses the Type I Interferon Response in SARS-CoV-2-Infected Cells. Vaccines 14 36560452
2024 Peptide Transporter 1-Mediated Dipeptide Transport Promotes Hepatocellular Carcinoma Metastasis by Activating MAP4K4/G3BP2 Signaling Axis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 9 38639383
2020 Correction to: Invasion-related circular RNA circFNDC3B inhibits bladder cancer progression through the miR-1178-3p/G3BP2/SRC/FAK axis. Molecular cancer 9 32772915
2024 Cooperative nuclear action of RNA-binding proteins PSF and G3BP2 to sustain neuronal cell viability is decreased in aging and dementia. Aging cell 8 39155453
2024 G3BP2 promotes tumor progression and gemcitabine resistance in PDAC via regulating PDIA3-DKC1-hENT in a stress granules-dependent manner. Acta pharmacologica Sinica 8 39289547
2024 Exosomal microRNA-363 mediates the destructive effect of M1 macrophages on chondrocytes by repressing G3BP2. Experimental cell research 7 39413984
2021 lncRNA XIST knockdown suppresses hypoxia/reoxygenation (H/R)-induced apoptosis of H9C2 cells by regulating miR-545-3p/G3BP2. IUBMB life 7 34060227
2023 Hsa_circRNA_001676 accelerates the proliferation, migration and stemness in colorectal cancer through regulating miR-556-3p/G3BP2 axis. Scientific reports 6 37884630
2025 Beyond Stress Granules: G3BP1 and G3BP2 Redundantly Suppress SARS-CoV-2 Infection. Viruses 4 40733530
2024 Hyperglycemia facilitates EV71 replication: Insights into miR-206-mediated regulation of G3BP2 promoting EV71 IRES activity. Theranostics 4 38773966
2022 G3BP2, a stress granule assembly factor, is dispensable for spermatogenesis in mice. PeerJ 4 35782098
2025 LINC2781 enhances antiviral immunity against coxsackievirus B5 infection by activating the JAK-STAT pathway and blocking G3BP2-mediated STAT1 degradation. mSphere 3 40626722
2024 A NOVEL CIRC_SUPT3/MIR-185-5P/G3BP2 CERNA NETWORK REGULATES HIGH GLUCOSE-INDUCED INJURY IN MOUSE PODOCYTE MPC5 CELLS. Shock (Augusta, Ga.) 2 38813926
2024 Identification of psoriasis-associated immune marker G3BP2 through single-cell RNA sequencing and meta analysis. Immunology 2 39267394
2026 Cereblon induces G3BP2 neosubstrate degradation using molecular surface mimicry. Nature structural & molecular biology 1 41559416
2025 ROBO1 enhanced esophageal carcinoma cell radioresistance through accelerating G3BP2-mediated eIF3A degradation. Cell death & disease 1 40188129
2025 LncRNA TDRG1 facilitates high glucose-induced retinal microvascular endothelial cell injury via miR-7-5p/G3BP2. In vitro cellular & developmental biology. Animal 1 40593275
2025 EPS8L2 drives colorectal cancer cell proliferation and migration via YBX1-dependent activation of G3BP2 transcription. Cell death & disease 1 40783393
2025 G3BP2 facilitates abnormal activation of fibroblast-like synoviocytes through p53 signaling pathway in rheumatoid arthritis. International immunopharmacology 1 41338150
2026 Research Progress on the Biological Function, Disease-Driving Mechanism and Clinical Targeting Strategies of G3BP2. Molecules (Basel, Switzerland) 0 41752399
2026 Circular RNA circMagi1 regulates the host immune response in respiratory Pseudomonas aeruginosa infection through G3BP2. mBio 0 41870066
2026 Long Non-Coding RNA Encoded by Infectious Bronchitis Virus Facilitates Viral Replication via Direct Interaction with G3BP2 and Expression Regulation of a Novel Host MicroRNA. Veterinary sciences 0 41893633
2026 An Analysis of G3BP2 in Non-Small Cell Lung Cancer. Cancers 0 41899571
2026 G3BP2-K76 acetylation promotes tumor immunoescape by stabilizing PD-L1 expression in colorectal cancer. Cell communication and signaling : CCS 0 41906099

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