Affinage

G3BP1

Ras GTPase-activating protein-binding protein 1 · UniProt Q13283

Length
466 aa
Mass
52.2 kDa
Annotated
2026-04-28
100 papers in source corpus 41 papers cited in narrative 40 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

G3BP1 is the central nucleating scaffold for cytoplasmic stress granule (SG) assembly, functioning as a molecular switch that undergoes RNA-dependent liquid-liquid phase separation (LLPS) upon cellular stress. In unstressed cells, G3BP1 adopts an auto-inhibited compact conformation stabilized by intramolecular electrostatic interactions between its acidic and arginine-rich intrinsically disordered regions; upon stress-induced polysome disassembly, freed mRNAs outcompete these auto-inhibitory contacts, triggering G3BP1 clustering and condensation, a process positively regulated by Caprin-1 binding and negatively regulated by USP10 binding at the NTF2-like domain, and further tuned by CK2-mediated Ser149 phosphorylation, PRMT1/5-mediated arginine methylation, CBP/p300-mediated K376 acetylation, TRIM21-catalyzed K63-linked ubiquitination, and FAF2-p97/VCP-dependent disassembly (PMID:32302571, PMID:32302572, PMID:27022092, PMID:27920254, PMID:27601476, PMID:31481451, PMID:34739333, PMID:36692217). Beyond SG biology, G3BP1 is a phosphorylation-dependent endoribonuclease that cleaves CA dinucleotides and cooperates with UPF1 in structure-mediated mRNA decay, and it promotes innate immune signaling by facilitating cGAS-DNA complex formation and enhancing RIG-I-dependent interferon production (PMID:11604510, PMID:32017897, PMID:30510222, PMID:30804210). The NTF2-like domain of G3BP1 is a convergent target exploited by diverse viruses—including alphaviruses and SARS-CoV-2—that bind via FGDF or ITFG motifs to disrupt SG-based antiviral defenses and co-opt G3BP1 for viral replication complex assembly (PMID:25658430, PMID:35240128, PMID:27509095).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2001 High

    Establishing G3BP1's intrinsic enzymatic activity resolved how it directly acts on RNA: it is a phosphorylation-dependent endoribonuclease with CA-dinucleotide specificity, and Ser149 phosphorylation controls its nuclear-cytoplasmic distribution.

    Evidence In vitro RNA cleavage assays with S149A/S149E mutants and subcellular fractionation in mammalian cells

    PMID:11604510

    Open questions at the time
    • Physiological substrates beyond c-myc mRNA not comprehensively identified
    • Structural basis of endoribonuclease catalysis unresolved
  2. 2007 High

    Identification of Caprin-1 as a direct NTF2-domain binding partner of G3BP1 that co-localizes in cytoplasmic RNA granules established the first protein interaction linking G3BP1 to mRNA granule biology.

    Evidence Co-IP, mutagenesis of Caprin-1 binding motif, colocalization in RNA granules associated with microtubules

    PMID:17210633

    Open questions at the time
    • Functional consequence for SG assembly not yet demonstrated at this point
    • Structural basis of Caprin-1/NTF2 interaction unknown
  3. 2012 High

    Demonstration that alphavirus nsP3 sequesters G3BP1 into viral replication complexes to prevent SG formation revealed that viruses exploit G3BP1 to counteract host antiviral granule defenses.

    Evidence Co-IP of viral nsP3 with G3BP1, nsP3 truncation mutants showing persistent SGs and viral attenuation

    PMID:23087212

    Open questions at the time
    • Binding motif on nsP3 not yet defined at atomic resolution
    • Whether other viral families use the same mechanism unknown
  4. 2013 High

    Crystal structures of the G3BP1 NTF2-like domain, alone and with FxFG peptide, revealed the binding groove architecture and specificity determinants for protein interactions that regulate SG formation and viral hijacking.

    Evidence X-ray crystallography at 1.6 Å and 3.3 Å resolution with ITC binding validation

    PMID:24324649

    Open questions at the time
    • No co-crystal with viral FGDF peptide yet obtained
    • How NTF2 dimerization affects binding cooperativity unclear
  5. 2015 High

    Definition of the FGDF motif as the common binding determinant for both cellular USP10 and diverse viral proteins on G3BP1's NTF2 domain unified the viral evasion and SG regulation mechanisms into a single structural framework.

    Evidence Co-IP and mutagenesis of FGDF motifs in USP10, SFV nsP3, and HSV ICP8; overexpression of FGDF-mutant USP10 fails to block SGs

    PMID:25658430

    Open questions at the time
    • Quantitative competition between USP10 and viral FGDF ligands not measured
    • SG regulation by USP10 FGDF binding not linked to its deubiquitinase activity
  6. 2016 High

    G3BP1/G3BP2 double knockout demonstrated that G3BP proteins are non-redundantly essential for SG formation, and mapped the opposing roles of Caprin-1 (promoter) and USP10 (inhibitor) as well as the requirement for the RGG domain's 40S ribosomal subunit interaction.

    Evidence CRISPR double KO with rescue by G3BP1 wild-type and mutants (S149E, F33W); Co-IP with 40S subunits

    PMID:27022092

    Open questions at the time
    • How 40S interaction mechanistically drives condensation unknown
    • Phosphomimetic S149E failure in rescue could reflect steric or electrostatic artifacts
  7. 2016 High

    Identification of PRMT1 and PRMT5 as arginine methyltransferases for G3BP1's RGG domain, with methylation serving as a reversible stress-responsive switch repressing SG assembly, added a second post-translational regulatory layer beyond Ser149 phosphorylation.

    Evidence Methylation assays with recombinant PRMTs, mass spectrometry of methylated residues, arsenite-induced demethylation kinetics

    PMID:27601476

    Open questions at the time
    • Identity of the demethylase(s) that remove arginine methylation upon stress unknown
    • Interplay between arginine methylation and Ser149 phosphorylation not addressed
  8. 2017 High

    Identification of CK2 as the kinase that phosphorylates G3BP1 Ser149 completed the writer-substrate relationship for the key phospho-switch controlling SG dynamics.

    Evidence In vitro kinase assay with purified CK2, chemical CK2 inhibition, and genetic depletion in cells

    PMID:27920254

    Open questions at the time
    • Phosphatase(s) that dephosphorylate Ser149 under stress not identified
    • Whether CK2 phosphorylates G3BP1 at additional sites unclear
  9. 2018 High

    G3BP1 was established as a co-activator of innate immune DNA sensing by physically interacting with cGAS and promoting formation of large cGAS-DNA complexes required for efficient interferon production, extending G3BP1's roles beyond SG biology.

    Evidence Co-IP, G3BP1 KO reducing IFN production, pharmacological disruption by EGCG, Aicardi-Goutières mouse model

    PMID:30510222

    Open questions at the time
    • Whether the cGAS-promoting function requires G3BP1 phase separation not determined
    • Domain on G3BP1 mediating cGAS interaction not mapped
  10. 2019 High

    Identification of K376 acetylation in the RRM domain as a modification that impairs RNA binding and is dynamically regulated by CBP/p300 (writer) and HDAC6 (eraser) revealed a third class of PTM regulating G3BP1's condensation competence.

    Evidence K376Q acetylation-mimetic mutagenesis, in vitro RNA binding assays, HDAC6/CBP inhibition, localization of acetylated G3BP1 outside SGs

    PMID:31481451

    Open questions at the time
    • Whether K376 acetylation affects endoribonuclease activity not tested
    • Stoichiometry of acetylated vs. unmodified G3BP1 in cells unknown
  11. 2020 High

    Reconstitution of G3BP1 LLPS in vitro demonstrated that G3BP1 is the minimal molecular switch for RNA-dependent phase separation, with three IDRs tuning condensation propensity and Caprin-1/USP10 modulating it through cooperative and anti-cooperative binding, respectively.

    Evidence In vitro LLPS reconstitution with purified components, IDR mutagenesis, phosphorylation perturbation, Caprin-1 and USP10 titration

    PMID:32302571 PMID:32302572

    Open questions at the time
    • Full-length G3BP1 structure in both auto-inhibited and RNA-bound states not yet solved
    • How the transition from liquid droplet to mature SG with distinct substructure occurs in cells not recapitulated
  12. 2020 High

    G3BP1 and UPF1 were shown to cooperate in a structure-mediated mRNA decay pathway that degrades mRNAs based on 3ʹ UTR secondary structure, revealing a non-SG function of G3BP1 in post-transcriptional gene regulation.

    Evidence RNA stability assays, reporter constructs with manipulated 3ʹ UTR structure, RNAi knockdown, RNA-seq

    PMID:32017897

    Open questions at the time
    • Whether G3BP1's endoribonuclease activity directly catalyzes this decay not determined
    • Structural features recognized by G3BP1-UPF1 not defined at single-nucleotide resolution
  13. 2021 High

    Demonstration that ubiquitination of G3BP1 recruits the FAF2-p97/VCP segregase to drive SG disassembly after heat shock established a mechanistic pathway for active granule clearance.

    Evidence Ubiquitination assays, Co-IP of ubiquitinated G3BP1 with FAF2/p97, KO and rescue experiments in human cells

    PMID:34739333

    Open questions at the time
    • Ubiquitin ligase responsible for this disassembly-linked ubiquitination not identified in this study
    • Whether p97/VCP unfolds G3BP1 or simply extracts it from the condensate unknown
  14. 2022 High

    Crystal structure of G3BP1 NTF2-like domain bound to SARS-CoV-2 N protein ITFG motif, combined with structure-guided mutagenesis showing loss of SG inhibition and reduced viral fitness, provided atomic-level understanding of how coronaviruses exploit the same G3BP1 surface groove as alphaviruses.

    Evidence X-ray crystallography, N-F17A mutagenesis, viral replication assay, in vivo pathology model

    PMID:35240128 PMID:38492217

    Open questions at the time
    • Whether ITFG motif competes with Caprin-1 or USP10 at the same subsite not resolved structurally
    • Therapeutic potential of blocking this interaction not validated in clinical settings
  15. 2023 High

    TRIM21 was identified as the E3 ligase catalyzing K63-linked ubiquitination of G3BP1 that directly inhibits LLPS in vitro, and autophagy receptors p62 and NDP52 were shown to mediate granulophagy at SG periphery, linking SG clearance to selective autophagy.

    Evidence E3 ligase screen, ubiquitination assays identifying K63 linkage, in vitro LLPS inhibition, KO of autophagy receptors

    PMID:36692217

    Open questions at the time
    • Relationship between TRIM21-mediated K63 ubiquitination and the FAF2-p97 disassembly pathway not clarified
    • Specific G3BP1 lysine residues targeted by TRIM21 not mapped
  16. 2023 High

    Crystal structure of G3BP1 NTF2 domain bound to Caprin-1 SLiM revealed a third binding site (His-31/His-62) distinct from the USP10-binding groove, and pH sensing within condensates was demonstrated, providing a structural basis for how Caprin-1 and USP10 exert non-competitive regulation.

    Evidence X-ray crystallography, ITC, nano-DSF, live-cell pHluorin2-G3BP1 pH reporter

    PMID:37161291

    Open questions at the time
    • Physiological significance of condensate acidification for SG maturation or clearance unknown
    • Whether pH-driven Caprin-1 release serves as a disassembly signal not tested
  17. 2024 Medium

    DCAF7 was identified as a scaffold facilitating USP10-mediated removal of K48-linked ubiquitin from G3BP1-K76, preventing proteasomal degradation and stabilizing SG-competent G3BP1 pools, revealing a second ubiquitin-linkage regulatory axis for G3BP1 homeostasis.

    Evidence Co-IP, K48 ubiquitination assay, K76 site-directed mutagenesis, DCAF7 knockdown rescue

    PMID:38973296

    Open questions at the time
    • E3 ligase writing K48-ubiquitin onto K76 not identified
    • Whether DCAF7/USP10 regulation operates during active stress or only basally not defined
    • Single lab without independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full-length structure of G3BP1 in both auto-inhibited and RNA-bound active states, the complete map of ubiquitin-modification sites and their interplay with other PTMs during the SG lifecycle, and the mechanistic basis of G3BP1's endoribonuclease activity in structure-mediated mRNA decay remain unresolved.
  • No full-length G3BP1 structure in either conformational state
  • Interplay among phosphorylation, methylation, acetylation, and ubiquitination during sequential SG assembly-maturation-disassembly not mapped
  • Catalytic mechanism and in vivo substrate repertoire of G3BP1 endoribonuclease activity largely unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 6 GO:0098772 molecular function regulator activity 4 GO:0140313 molecular sequestering activity 3 GO:0140098 catalytic activity, acting on RNA 2
Localization
GO:0031410 cytoplasmic vesicle 5 GO:0005829 cytosol 4
Pathway
R-HSA-8953897 Cellular responses to stimuli 8 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-8953854 Metabolism of RNA 2
Partners
CAPRIN-1CGASDCAF7FAF2TRIM21UBAP2LUPF1USP10
Complex memberships
G3BP1-Caprin-1 RNPcGAS-G3BP1 complexstress granule

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2020 G3BP1 functions as a molecular switch that triggers RNA-dependent liquid-liquid phase separation (LLPS) to assemble stress granules. Three distinct intrinsically disordered regions (IDRs) in G3BP1 regulate its intrinsic propensity for LLPS, fine-tuned by phosphorylation within the IDRs. Binding of Caprin1 (positive cooperativity) or USP10 (negative cooperativity) further regulates SG assembly through the core G3BP1-RNA interaction network. In vitro LLPS reconstitution, mutagenesis of IDRs, phosphorylation analysis, binding assays with Caprin1/USP10 Cell High 32302571
2020 Under non-stress conditions, G3BP1 adopts a compact auto-inhibited state stabilized by intramolecular electrostatic interactions between its intrinsically disordered acidic tracts and positively charged arginine-rich region. Upon stress, free mRNAs outcompete these auto-inhibitory interactions, inducing a conformational transition that facilitates G3BP1 clustering through protein-RNA interactions, driving condensation. Biochemical assays, NMR/structural analysis, RNA competition assays, LLPS reconstitution Cell High 32302572
2016 G3BP1 and G3BP2 double knockout abolishes stress granule formation in response to eIF2α phosphorylation or eIF4A inhibition. Phosphomimetic G3BP1-S149E fails to rescue SG formation. G3BP1-F33W (unable to bind Caprin1 or USP10) can still rescue SG formation. Caprin1 binding promotes and USP10 binding inhibits SG formation. G3BP1 interacts with 40S ribosomal subunits through its RGG motif, required for SG formation. CRISPR/siRNA double KO, rescue with G3BP1 mutants, Co-IP with 40S subunits The Journal of cell biology High 27022092
2001 G3BP1 is a phosphorylation-dependent endoribonuclease that cleaves RNA exclusively between cytosine and adenine (CA dinucleotides) via its C-terminal RRM-type RNA binding motif. Phosphorylation at serine 149 controls subcellular localization: S149A mutant remains cytoplasmic; S149E (phosphomimetic) translocates to the nucleus. G3BP1 binds c-myc mRNA and modulates its decay. In vitro RNA cleavage assays, site-directed mutagenesis (S149A, S149E), subcellular fractionation, RNase activity characterization Molecular and cellular biology High 11604510
2021 Stress granule disassembly after heat shock specifically requires ubiquitination of G3BP1. Ubiquitinated G3BP1 interacts with the ER-associated protein FAF2, which engages the ubiquitin-dependent segregase p97/VCP, thereby weakening the SG interaction network and driving disassembly. Ubiquitination assays in human cells, Co-IP of ubiquitinated G3BP1 with FAF2/p97, KO and rescue experiments Science High 34739333
2013 Crystal structures of the human G3BP1 NTF2-like domain alone and in complex with FxFG nucleoporin repeat peptide reveal that the FxFG binding site is located between two alpha helices (not at the dimer interface as in NTF2). ITC studies showed specificity toward FxFG motif but not FG or GLFG motifs. X-ray crystallography (1.6 Å and 3.3 Å), isothermal titration calorimetry (ITC) PloS one High 24324649
2015 Viral proteins from Semliki Forest virus (SFV), herpes simplex virus ICP8, and cellular USP10 all bind the NTF2-like domain of G3BP1 via an FGDF motif (both phenylalanine and glycine residues required). Overexpression of wild-type but not FGDF-mutant USP10 blocks SG assembly. A structural model of G3BP1 NTF2 domain bound to FGDF peptide was presented. Co-IP, mutagenesis of FGDF motifs, overexpression functional assays, structural modeling PLoS pathogens High 25658430
2018 G3BP1 physically interacts with cGAS and promotes DNA binding of cGAS by facilitating formation of large cGAS complexes, thereby enhancing cGAS-dependent interferon production. G3BP1 deficiency leads to inefficient cGAS-DNA binding and reduced IFN production. EGCG disrupts existing G3BP1-cGAS complexes and inhibits DNA-triggered cGAS activation. Co-IP, knockdown/KO functional assays, in vitro binding assays, mouse model of Aicardi-Goutières syndrome Nature immunology High 30510222
2016 G3BP1 arginine residues in its RGG domain are methylated by PRMT1 and PRMT5. Increased arginine methylation represses SG assembly, while decreased methylation promotes it. Arsenite stress rapidly and reversibly decreases asymmetric arginine methylation on G3BP1, acting as a regulatory signal for SG formation. Arginine methylation assays, PRMT1/PRMT5 biochemical experiments, SG formation assays with methylation inhibitors, mass spectrometry identification of methylated residues The Journal of biological chemistry High 27601476
2017 Casein kinase 2 (CK2) phosphorylates G3BP1 at serine 149 in vitro and in cells. CK2 activity promotes stress granule disassembly; CK2 inhibition or depletion alters SG dynamics. In vitro kinase assay with CK2 and G3BP1, chemical CK2 inhibition, genetic depletion, overexpression functional assays Molecular and cellular biology High 27920254
2007 Caprin-1 binds to the NTF2-like domain of G3BP1 through a highly conserved motif F(M/I/L)Q(D/E)Sx(I/L)D. Caprin-1 carboxy-terminal region binds c-Myc and cyclin D2 mRNAs via RGG motifs. Caprin-1/G3BP-1 complex localizes to cytoplasmic RNA granules associated with microtubules, concentrated at leading and trailing edges of migrating cells. Co-IP, mutagenesis of Caprin-1 RGG motifs, colocalization by immunofluorescence, mRNA binding assays Molecular and cellular biology High 17210633
2020 G3BP1 and UPF1 are required for a structure-mediated RNA decay pathway that degrades mRNAs based on overall 3' UTR secondary structure (independent of specific sequence). Depletion of either protein increased steady-state levels of mRNAs with highly structured 3' UTRs and highly structured circular RNAs. RNA stability assays, reporter constructs with structural manipulation, RNAi knockdown of G3BP1 and UPF1, RNA-seq Molecular cell High 32017897
2019 Lysine 376 (K376) of G3BP1 within the RRM RNA binding domain is acetylated, which impairs RNA binding. K376 acetylation also impairs G3BP1 interaction with PABP1 but not with Caprin-1 or USP10. K376 acetylation is regulated by HDAC6 (eraser) and CBP/p300 (writer), and K376-acetylated G3BP1 is found outside SGs during SG resolution. Site-directed mutagenesis (K376Q acetylation-mimetic), in vitro RNA binding assays, Co-IP, HDAC6/CBP inhibition, endogenous acetylation detection Molecular and cellular biology High 31481451
2023 TRIM21 E3 ubiquitin ligase catalyzes K63-linked ubiquitination of G3BP1, and this ubiquitination inhibits LLPS in vitro. Autophagy receptors SQSTM1/p62 and CALCOCO2/NDP52 directly interact with G3BP1 at the SG periphery and mediate SG elimination. Ubiquitination assays, LLPS inhibition in vitro, E3 ligase screen, Co-IP, KO of autophagy receptors Autophagy High 36692217
2011 Arginine methylation of G3BP1 in response to Wnt3a signaling regulates β-catenin (Ctnnb1) mRNA. G3BP1 is a Ctnnb1 mRNA binding protein identified by mass spectrometry of a Dishevelled-associated, arginine-methylated complex. Methylation of G3BP1 acts as a molecular switch regulating β-catenin mRNA in response to Wnt3a. Mass spectrometry, RNA immunoprecipitation, Wnt3a stimulation assay, arginine methylation analysis Journal of cell science Medium 21652632
2012 Poly(ADP-ribose) (pADPr) binds to the glycine-arginine-rich (RGG) domain of G3BP1, as shown by peptide pADPr blot assay. pADPr is required for G3BP1-mediated SG assembly following genotoxic stress and modulates nuclear translocation of G3BP1; co-transfection of PARG (pADPr glycohydrolase) with G3BP1 inhibits SG formation. Quantitative proteomics (pADPr-associated complexes), peptide pADPr binding assay, live cell imaging, co-transfection functional assays Journal of cell science Medium 22767504
2007 G3BP1 and G3BP2 bind to p53 in vitro and in vivo, and G3BP expression leads to redistribution of p53 from nucleus to cytoplasm. G3BP2 associates additionally with MDM2 and reduces MDM2-mediated p53 ubiquitylation and degradation. shRNA knockdown of G3BP1 or G3BP2 upregulates p53 levels and activity. Co-IP, proteomic approach, ubiquitination assays, shRNA knockdown Oncogene Medium 17297477
2010 G3BP1 directly binds the 3' UTR of beta-F1-ATPase (ATP5B) mRNA via immunoprecipitation and RNA-bridged trimolecular fluorescence complementation. This interaction inhibits beta-F1-ATPase mRNA translation at the initiation level; the beta-F1-RNP complex is sorted to the periphery of mitochondria. Affinity chromatography, RNA-IP, TriFC assay, confocal and immunoelectron microscopy, translation inhibition assay Journal of cell science Medium 20663914
2018 G3BP1 binds viral dsRNA and RIG-I via its C-terminal RGG domain. G3BP1 enhances RIG-I-induced IFN-β production; overexpression of G3BP1 with RIG-I significantly increases ifn-b mRNA synthesis. G3BP1 co-localizes with RIG-I and infecting VSV. Co-IP, biotin-labeled dsRNA/poly(I:C) pulldown, in vitro translated G3BP1 binding assay, confocal colocalization, overexpression functional assay The Journal of biological chemistry Medium 30804210
2015 G3BP1 promotes stress-induced interactions between stress granules and processing bodies (SG-PB docking). Depletion of G3BP1 or its upstream regulator TDP-43 decreases SG size, reduces SG-PB docking, and impairs preservation of polyadenylated mRNA. Reintroduction of G3BP1 alone rescues all phenotypes. siRNA knockdown, rescue experiments, live-cell imaging of SG-PB interactions, poly(A) mRNA preservation assay The Journal of cell biology Medium 25847539
2018 G3BP1 aggregates within peripheral nerve axons in stress granule-like structures that decrease during regeneration. Phosphorylated G3BP1 is increased during regeneration. Disrupting G3BP1 function by overexpressing a dominant-negative protein activates intra-axonal mRNA translation, increases axon growth, disassembles axonal SG-like structures, and accelerates rat nerve regeneration in vivo. Dominant-negative overexpression, immunofluorescence colocalization, in vitro axon growth assay, in vivo rat nerve regeneration model Nature communications High 30135423
2020 After peripheral nerve injury, CK2α phosphorylates G3BP1 at Ser149, triggering G3BP1 granule disassembly in injured axons. CK2α is itself locally translated from Csnk2a1 mRNA in axons after injury in a Ca2+-dependent manner. Phosphomimetic G3BP1 shows decreased RNA binding in DRG neurons compared to wild-type or non-phosphorylatable G3BP1. Dual FRAP reporter assay for axonal translation, Ca2+ chelation/ER Ca2+ release experiments, Csnk2a1 mRNA depletion, phosphomimetic G3BP1 RNA binding assay Current biology Medium 33065005
2020 UBAP2L forms distinct cores that act upstream of G3BP1 in stress granule nucleation. UBAP2L occupies different domains inside SGs from G3BP1, forms granules independent of G3BP1/2, and is required for SG assembly across multiple stress conditions. UBAP2L facilitates G3BP1 core formation and SG assembly/growth. Super-resolution and expansion microscopy, CRISPR KO of UBAP2L and G3BP1/2, cell biology epistasis experiments Current biology Medium 31956030
2012 G3BP1 NSP3 interaction (Semliki Forest virus C-terminal domain) sequesters G3BP1 into viral RNA replication complexes, preventing SG formation on viral mRNAs. A viral nsP3 C-terminal truncation mutant induces more persistent SGs and is attenuated for propagation. nsP3/G3BP1 interaction also blocks SGs induced by non-viral stresses. Co-IP of viral nsP3 with G3BP1, viral mutant analysis, SG formation assays, viral propagation assays Molecular biology of the cell High 23087212
2010 MK-STYX (pseudophosphatase) binds G3BP1 and inhibits SG formation; binding is reduced for the catalytically active MK-STYX mutant. The active MK-STYX mutant can dephosphorylate G3BP1. MK-STYX inhibits G3BP1-induced SG formation independently of G3BP1 Ser149 phosphorylation. Mass spectrometry identification, Co-IP, SG formation assay, site-directed mutagenesis generating active pseudophosphatase The Biochemical journal Medium 20180778
2020 G3BP1 promotes intermolecular RNA-RNA interactions (acts as an 'RNA condenser'), facilitating assembly of RNA condensates. Following stress granule formation, G3BP1 is dispensable for the RNA component of granules to persist in vitro and in cells when RNA decondensers are inactivated, indicating a 'condensate chaperone' function that promotes initial condensation. In vitro RNA condensation assays, G3BP1 depletion, RNA granule persistence assays in cells Molecular cell Medium 39637853
2021 G3BP1 promotes pre-condensation of cGAS into a primary liquid-phase condensation state in resting cells, enabling rapid cGAS response to DNA. G3BP1 deletion diminishes cGAS particle formation and DNA-induced LLPS. DNA (but not RNA) treatment dissociates G3BP1 from cGAS. RNA does not activate cGAS despite forming condensates with it. High-resolution microscopy, G3BP1 KO cells, LLPS assays, Co-IP, G3BP1 pharmacological inhibition EMBO reports Medium 34779554
2023 SIRT2 deacetylates G3BP1 at K257, K276, and K376, leading to disassembly of the cGAS-G3BP1 complex and inhibiting cGAS DNA binding and droplet formation, thereby negatively regulating the cGAS-STING pathway. SIRT2 inhibition elevates IFN expression and protects mice from HSV-1 infection. Co-IP, deacetylation assay, cGAS-G3BP1 complex disruption assay, LLPS/droplet formation assay, site-directed mutagenesis of G3BP1 acetylation sites, in vivo mouse HSV-1 model EMBO reports Medium 37870259
2019 eIF4GI interacts with G3BP1 through aa 182-203 of eIF4GI and the RNA-binding domain of G3BP1, and this interaction is required for typical stress granule formation. Picornavirus 2A or L proteins disrupt the eIF4GI-G3BP1 interaction to block SG formation. Co-IP with truncation mutants, rescue of SG formation by eIF4GI, viral protein-mediated disruption of complex Cell discovery Medium 30603102
2022 The SARS-CoV-2 nucleocapsid (N) protein interacts with G3BP1 via an ITFG motif (residue F17) in N protein, binding a conserved surface groove of the G3BP1 NTF2-like domain. N-F17A mutation causes specific loss of G3BP1/2 interaction, abolishes N protein inhibition of SG assembly, decreases viral replication, and reduces pathology in vivo. Crystal structure of G3BP1-NTF2 with N protein peptide, biochemical interaction assays, structure-guided mutagenesis, viral replication assay, in vivo pathology model Journal of molecular biology High 35240128 38492217
2023 SARS-CoV-2 N protein disrupts the cGAS-G3BP1 complex via DNA-induced LLPS of N protein, impairing cGAS DNA recognition and IFN-I signaling. N protein undergoes phase separation to sequester G3BP1 away from cGAS. Co-IP, LLPS assay, cGAS-DNA binding assay, IFN-I signaling readout in infected cells Signal transduction and targeted therapy Medium 37100798
2024 DCAF7 serves as a scaffold that facilitates interaction between USP10 and G3BP1, leading to elimination of K48-linked ubiquitin from Lys76 of G3BP1, preventing its proteasomal degradation and promoting stress granule-like structure formation. Co-IP, ubiquitination assay (K48-linkage), site-directed mutagenesis (K76 on G3BP1), KD of G3BP1 rescuing DCAF7 effects Advanced science Medium 38973296
2016 Old World alphaviruses (Chikungunya, Sindbis viruses) exploit G3BP family proteins for assembly of viral replication complexes through interactions between FGDF-like repeating amino acid sequences in the C-terminus of viral nsP3 and G3BP proteins. Both RNA-binding and self-assembly abilities of G3BP are key characteristics enabling their role in alphavirus replication. KO of G3BP family members, viral replication assays, interaction mapping of nsP3 C-terminal sequences PLoS pathogens Medium 27509095
2019 G3BP1 NTF2-like and RGG domains are both necessary for formation of a complex between alphavirus nsP3, G3BP1, and the 40S ribosomal subunit (confirmed by Co-IP). The NTF2-like domain mediates nsP3:G3BP1 interaction required for clustering of cytopathic vacuoles; the RGG domain enables G3BP1-mediated recruitment of translation initiation machinery and accumulation of electron-dense material surrounding viral replication complexes. CRISPR KO reconstitution with G3BP1 mutants/truncations, Co-IP of 40S/nsP3/G3BP1 complex, electron microscopy, ribopuromycylation translation assay PLoS pathogens Medium 31199850
2020 G3BP1 depletion or its upstream regulator TDP-43 depletion disturbs normal SG-processing body interactions and impairs preservation of polyadenylated mRNA. TDP-43 directly binds a conserved cis regulatory element in the 3' UTR of G3BP1 mRNA to stabilize it; nuclear TDP-43 depletion reduces G3BP1 protein levels in vitro and in vivo. RIP (RNA immunoprecipitation) of TDP-43 on G3BP1 3'UTR, siRNA knockdown, in vivo mouse neuronal experiments, ALS/FTD patient tissue analysis Brain Medium 34115105
2021 G3BP1 inhibits SPOP E3 ubiquitin ligase (Cul3SPOP) function as a competitive inhibitor. G3BP1-SPOP interaction was identified by Co-IP, and AR directly upregulates G3BP1 transcription in a feed-forward manner. Loss of G3BP1-mediated SPOP inhibition allows substrate degradation, suppressing AR signaling. Co-IP, transcriptomic analysis, functional ubiquitination assays, AR ChIP, competitive inhibition of Cul3SPOP by G3BP1 Nature communications Medium 34795264
2021 G3BP1 interacts with and inactivates GSK-3β, suppressing β-catenin phosphorylation and proteasomal degradation, thus stabilizing β-catenin and activating β-catenin target genes to promote breast cancer cell proliferation. Co-IP of G3BP1 and GSK-3β, GSK-3β kinase activity assay, β-catenin ubiquitination/stability assay, disruption of G3BP1-GSK-3β interaction Acta pharmacologica Sinica Medium 33536604
2015 YB-1 directly binds the 5' UTR of G3BP1 mRNA and translationally activates it, controlling G3BP1 protein availability for SG nucleation. YB-1 inactivation dramatically reduces G3BP1 levels and SG formation in sarcoma cells. RNA-IP, luciferase 5'UTR reporter assay, YB-1 knockdown with G3BP1 rescue, in vivo xenograft model The Journal of cell biology Medium 25800057
2023 Crystal structure of G3BP1 NTF2-like domain in complex with a Caprin-1-derived short linear motif (SLiM) reveals that Caprin-1 interacts with His-31 and His-62 in a third NTF2-binding site distinct from the USP10-binding site. G3BP1/USP10 complex is more resistant to acidic pH than G3BP1/Caprin-1, and acidification of condensates by ~0.5 pH units relative to cytosol was detected by pHluorin2-G3BP1 fusion. X-ray crystallography, nano-DSF, biochemical binding assays, ITC, live-cell pH reporter (pHluorin2-G3BP1) Open biology High 37161291
2024 Two small molecules (G3Ia and G3Ib) designed to bind a specific pocket in G3BP1/2 (the same pocket targeted by viral FGDF inhibitors) disrupt co-condensation of RNA, G3BP1, and Caprin-1 in vitro, inhibit SG formation in cells, and dissolve pre-existing stress granules. Structure-based drug design, in vitro LLPS/co-condensation assay, cell SG formation assay with multiple stressors The Journal of cell biology Medium 38284934

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 G3BP1 Is a Tunable Switch that Triggers Phase Separation to Assemble Stress Granules. Cell 971 32302571
2020 RNA-Induced Conformational Switching and Clustering of G3BP Drive Stress Granule Assembly by Condensation. Cell 652 32302572
2016 G3BP-Caprin1-USP10 complexes mediate stress granule condensation and associate with 40S subunits. The Journal of cell biology 507 27022092
2018 A G3BP1-Interacting lncRNA Promotes Ferroptosis and Apoptosis in Cancer via Nuclear Sequestration of p53. Cancer research 412 29588351
2021 Ubiquitination of G3BP1 mediates stress granule disassembly in a context-specific manner. Science (New York, N.Y.) 253 34739333
2012 Both G3BP1 and G3BP2 contribute to stress granule formation. Genes to cells : devoted to molecular & cellular mechanisms 249 23279204
2018 G3BP1 promotes DNA binding and activation of cGAS. Nature immunology 247 30510222
2015 YB-1 regulates stress granule formation and tumor progression by translationally activating G3BP1. The Journal of cell biology 221 25800057
2007 Distinct structural features of caprin-1 mediate its interaction with G3BP-1 and its induction of phosphorylation of eukaryotic translation initiation factor 2alpha, entry to cytoplasmic stress granules, and selective interaction with a subset of mRNAs. Molecular and cellular biology 217 17210633
2020 Structure-Mediated RNA Decay by UPF1 and G3BP1. Molecular cell 215 32017897
2012 Contrasting pathology of the stress granule proteins TIA-1 and G3BP in tauopathies. The Journal of neuroscience : the official journal of the Society for Neuroscience 199 22699908
2001 RasGAP-associated endoribonuclease G3Bp: selective RNA degradation and phosphorylation-dependent localization. Molecular and cellular biology 167 11604510
2016 Arginine Demethylation of G3BP1 Promotes Stress Granule Assembly. The Journal of biological chemistry 163 27601476
2016 New World and Old World Alphaviruses Have Evolved to Exploit Different Components of Stress Granules, FXR and G3BP Proteins, for Assembly of Viral Replication Complexes. PLoS pathogens 156 27509095
2012 Sequestration of G3BP coupled with efficient translation inhibits stress granules in Semliki Forest virus infection. Molecular biology of the cell 150 23087212
2018 Axonal G3BP1 stress granule protein limits axonal mRNA translation and nerve regeneration. Nature communications 139 30135423
2015 Stress granule components G3BP1 and G3BP2 play a proviral role early in Chikungunya virus replication. Journal of virology 134 25653451
2015 Viral and cellular proteins containing FGDF motifs bind G3BP to block stress granule formation. PLoS pathogens 127 25658430
2004 Rasputin, more promiscuous than ever: a review of G3BP. The International journal of developmental biology 127 15602692
2019 The stress granule protein G3BP1 binds viral dsRNA and RIG-I to enhance interferon-β response. The Journal of biological chemistry 110 30804210
2012 Endogenous TDP-43, but not FUS, contributes to stress granule assembly via G3BP. Molecular neurodegeneration 104 23092511
2015 G3BP1 promotes stress-induced RNA granule interactions to preserve polyadenylated mRNA. The Journal of cell biology 99 25847539
2020 UBAP2L Forms Distinct Cores that Act in Nucleating Stress Granules Upstream of G3BP1. Current biology : CB 94 31956030
2023 Stress granule homeostasis is modulated by TRIM21-mediated ubiquitination of G3BP1 and autophagy-dependent elimination of stress granules. Autophagy 90 36692217
2016 ALS mutant SOD1 interacts with G3BP1 and affects stress granule dynamics. Acta neuropathologica 90 27481264
2017 Casein Kinase 2 Is Linked to Stress Granule Dynamics through Phosphorylation of the Stress Granule Nucleating Protein G3BP1. Molecular and cellular biology 81 27920254
2005 Control of fetal growth and neonatal survival by the RasGAP-associated endoribonuclease G3BP. Molecular and cellular biology 76 16166649
2019 The Acetylation of Lysine-376 of G3BP1 Regulates RNA Binding and Stress Granule Dynamics. Molecular and cellular biology 75 31481451
2001 G3BP is overexpressed in human tumors and promotes S phase entry. Cancer letters 75 11146228
2007 Modulation of p53 and MDM2 activity by novel interaction with Ras-GAP binding proteins (G3BP). Oncogene 74 17297477
2020 G3BP1 controls the senescence-associated secretome and its impact on cancer progression. Nature communications 73 33020468
2012 Quantitative proteomics and dynamic imaging reveal that G3BP-mediated stress granule assembly is poly(ADP-ribose)-dependent following exposure to MNNG-induced DNA alkylation. Journal of cell science 72 22767504
2014 eEF2 and Ras-GAP SH3 domain-binding protein (G3BP1) modulate stress granule assembly during HIV-1 infection. Nature communications 71 25229650
2011 Intracellular CD24 inhibits cell invasion by posttranscriptional regulation of BART through interaction with G3BP. Cancer research 71 21266361
2011 Arginine methylation of G3BP1 in response to Wnt3a regulates β-catenin mRNA. Journal of cell science 71 21652632
2021 The stress granule protein G3BP1 promotes pre-condensation of cGAS to allow rapid responses to DNA. EMBO reports 64 34779554
2010 Human G3BP1 interacts with beta-F1-ATPase mRNA and inhibits its translation. Journal of cell science 64 20663914
2019 Separate domains of G3BP promote efficient clustering of alphavirus replication complexes and recruitment of the translation initiation machinery. PLoS pathogens 62 31199850
2002 Heregulin induces expression, ATPase activity, and nuclear localization of G3BP, a Ras signaling component, in human breast tumors. Cancer research 62 11888885
2021 The multi-functional RNA-binding protein G3BP1 and its potential implication in neurodegenerative disease. Journal of neurochemistry 61 33349931
2010 Tudor-SN interacts with and co-localizes with G3BP in stress granules under stress conditions. FEBS letters 61 20643132
2020 Translational Repression of G3BP in Cancer and Germ Cells Suppresses Stress Granules and Enhances Stress Tolerance. Molecular cell 57 32692974
2013 Regulation of PMP22 mRNA by G3BP1 affects cell proliferation in breast cancer cells. Molecular cancer 56 24321297
2021 Research Progress on the Structure and Function of G3BP. Frontiers in immunology 55 34526993
2019 Loss of G3BP1 suppresses proliferation, migration, and invasion of esophageal cancer cells via Wnt/β-catenin and PI3K/AKT signaling pathways. Journal of cellular physiology 55 30989663
2013 Crystal structures of the human G3BP1 NTF2-like domain visualize FxFG Nup repeat specificity. PloS one 54 24324649
2019 SG formation relies on eIF4GI-G3BP interaction which is targeted by picornavirus stress antagonists. Cell discovery 52 30603102
2021 Huntington's disease mice and human brain tissue exhibit increased G3BP1 granules and TDP43 mislocalization. The Journal of clinical investigation 51 33945510
2018 The roles and mechanisms of G3BP1 in tumour promotion. Journal of drug targeting 51 30207743
2021 TDP-43 stabilizes G3BP1 mRNA: relevance to amyotrophic lateral sclerosis/frontotemporal dementia. Brain : a journal of neurology 48 34115105
2020 G3BP1-linked mRNA partitioning supports selective protein synthesis in response to oxidative stress. Nucleic acids research 48 32406909
2024 Interaction between host G3BP and viral nucleocapsid protein regulates SARS-CoV-2 replication and pathogenicity. Cell reports 47 38492217
2016 The stress granule component G3BP is a novel interaction partner for the nuclear shuttle proteins of the nanovirus pea necrotic yellow dwarf virus and geminivirus abutilon mosaic virus. Virus research 46 27693920
2016 G3BP1 contributes to tumor metastasis via upregulation of Slug expression in hepatocellular carcinoma. American journal of cancer research 46 27904777
2011 Revisiting G3BP1 as a RasGAP binding protein: sensitization of tumor cells to chemotherapy by the RasGAP 317-326 sequence does not involve G3BP1. PloS one 45 22205990
2024 Identification of small molecule inhibitors of G3BP-driven stress granule formation. The Journal of cell biology 44 38284934
2023 Phase-separated nucleocapsid protein of SARS-CoV-2 suppresses cGAS-DNA recognition by disrupting cGAS-G3BP1 complex. Signal transduction and targeted therapy 44 37100798
2020 A Ca2+-Dependent Switch Activates Axonal Casein Kinase 2α Translation and Drives G3BP1 Granule Disassembly for Axon Regeneration. Current biology : CB 44 33065005
2020 G3BP1 interacts with YWHAZ to regulate chemoresistance and predict adjuvant chemotherapy benefit in gastric cancer. British journal of cancer 43 32989225
2017 G3BP1 interacts directly with the FMDV IRES and negatively regulates translation. The FEBS journal 43 28755480
2011 The N-terminal domain of G3BP enhances cell motility and invasion by posttranscriptional regulation of BART. Molecular cancer research : MCR 42 21665939
2020 Norovirus infection results in eIF2α independent host translation shut-off and remodels the G3BP1 interactome evading stress granule formation. PLoS pathogens 41 31905230
2010 The pseudophosphatase MK-STYX interacts with G3BP and decreases stress granule formation. The Biochemical journal 40 20180778
2022 SARS-CoV-2 Nucleocapsid Protein Targets a Conserved Surface Groove of the NTF2-like Domain of G3BP1. Journal of molecular biology 39 35240128
2022 The roles of G3BP1 in human diseases (review). Gene 38 35176431
2017 Mammalian Orthoreovirus Factories Modulate Stress Granule Protein Localization by Interaction with G3BP1. Journal of virology 37 28794026
2023 KIF14 promotes proliferation, lymphatic metastasis and chemoresistance through G3BP1/YBX1 mediated NF-κB pathway in cholangiocarcinoma. Oncogene 36 36922675
2024 G3BP1 promotes intermolecular RNA-RNA interactions during RNA condensation. Molecular cell 32 39637853
2022 G3BP1 coordinates lysophagy activity to protect against compression-induced cell ferroptosis during intervertebral disc degeneration. Cell proliferation 32 36450665
2021 G3BP1 inhibits Cul3SPOP to amplify AR signaling and promote prostate cancer. Nature communications 31 34795264
2023 Pro-Viral and Anti-Viral Roles of the RNA-Binding Protein G3BP1. Viruses 30 36851663
2021 G3BP1 promotes human breast cancer cell proliferation through coordinating with GSK-3β and stabilizing β-catenin. Acta pharmacologica Sinica 30 33536604
2020 Depletion of lncRNA MALAT1 inhibited sunitinib resistance through regulating miR-362-3p-mediated G3BP1 in renal cell carcinoma. Cell cycle (Georgetown, Tex.) 29 32663095
2011 Analysis of subcellular G3BP redistribution during rubella virus infection. The Journal of general virology 29 21994324
2020 Seneca Valley Virus 3C Protease Inhibits Stress Granule Formation by Disrupting eIF4GI-G3BP1 Interaction. Frontiers in immunology 28 33133097
2019 G3BP1 inhibits ubiquitinated protein aggregations induced by p62 and USP10. Scientific reports 28 31501480
2023 SIRT2 negatively regulates the cGAS-STING pathway by deacetylating G3BP1. EMBO reports 27 37870259
2019 GTPase-activating protein-binding protein 1 (G3BP1) plays an antiviral role against porcine epidemic diarrhea virus. Veterinary microbiology 27 31500725
2023 The stress granule protein G3BP1 alleviates spinocerebellar ataxia-associated deficits. Brain : a journal of neurology 26 36511898
2022 TDRD3 is an antiviral restriction factor that promotes IFN signaling with G3BP1. PLoS pathogens 26 35085371
2021 Circ_0119872 promotes uveal melanoma development by regulating the miR-622/G3BP1 axis and downstream signalling pathways. Journal of experimental & clinical cancer research : CR 26 33579337
2020 Sensitivity of Alphaviruses to G3BP Deletion Correlates with Efficiency of Replicase Polyprotein Processing. Journal of virology 26 31941782
2019 G3BP1 activates the TGF-β/Smad signaling pathway to promote gastric cancer. OncoTargets and therapy 26 31564899
2015 Interaction and colocalization of HERMES/RBPMS with NonO, PSF, and G3BP1 in neuronal cytoplasmic RNP granules in mouse retinal line cells. Genes to cells : devoted to molecular & cellular mechanisms 26 25651939
2023 G3BP1 and SLU7 Jointly Promote Immune Evasion by Downregulating MHC-I via PI3K/Akt Activation in Bladder Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 25 38084438
2021 Genomics-guided targeting of stress granule proteins G3BP1/2 to inhibit SARS-CoV-2 propagation. International journal of biological macromolecules 25 34517025
2012 The pseudophosphatase MK-STYX inhibits stress granule assembly independently of Ser149 phosphorylation of G3BP-1. The FEBS journal 25 23163895
2015 G3BP1 restricts HIV-1 replication in macrophages and T-cells by sequestering viral RNA. Virology 24 26432022
2010 Structure-based design of peptides against G3BP with cytotoxicity on tumor cells. Journal of chemical information and modeling 24 20180532
2023 G3BP1-dependent mechanism suppressing protein aggregation in Huntington's models and its demise upon stress granule assembly. Human molecular genetics 23 36611004
2022 Upregulated LINC01088 facilitates malignant phenotypes and immune escape of colorectal cancer by regulating microRNAs/G3BP1/PD-L1 axis. Journal of cancer research and clinical oncology 22 35357586
2023 SERBP1 Promotes Stress Granule Clearance by Regulating 26S Proteasome Activity and G3BP1 Ubiquitination and Protects Male Germ Cells from Thermostimuli Damage. Research (Washington, D.C.) 21 37223481
2021 Analyzing the G3BP-like gene family of Arabidopsis thaliana in early turnip mosaic virus infection. Scientific reports 21 33500425
2023 Caprin-1 binding to the critical stress granule protein G3BP1 is influenced by pH. Open biology 20 37161291
2022 CircEIF3H-IGF2BP2-HuR scaffold complex promotes TNBC progression via stabilizing HSPD1/RBM8A/G3BP1 mRNA. Cell death discovery 20 35568705
2020 Overexpression of G3BP1 facilitates the progression of colon cancer by activating β‑catenin signaling. Molecular medicine reports 20 33000280
2019 G3BP1 Depletion Increases Radiosensitisation by Inducing Oxidative Stress in Response to DNA Damage. Anticancer research 20 31704836
2016 Preferential binding of a stable G3BP ribonucleoprotein complex to intron-retaining transcripts in mouse brain and modulation of their expression in the cerebellum. Journal of neurochemistry 20 27513819
1999 Upregulation of the RAS-GTPase activating protein (GAP)-binding protein (G3BP) in proliferating RPE cells. Journal of cellular biochemistry 19 10404389
2024 DCAF7 Acts as A Scaffold to Recruit USP10 for G3BP1 Deubiquitylation and Facilitates Chemoresistance and Metastasis in Nasopharyngeal Carcinoma. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 18 38973296