Affinage

EIF4G1

Eukaryotic translation initiation factor 4 gamma 1 · UniProt Q04637

Length
1599 aa
Mass
175.5 kDa
Annotated
2026-06-09
100 papers in source corpus 44 papers cited in narrative 44 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EIF4G1 is a large modular scaffold that organizes the eIF4F cap-binding complex and bridges mRNA to the 40S ribosome to drive both cap-dependent and cap-independent translation initiation (PMID:7665619, PMID:10469664). Domain dissection by picornaviral proteases established its tripartite architecture: an N-terminal region binding eIF4E, a central region binding eIF3 and eIF4A, and a C-terminal regulatory third (PMID:7665619), with a conserved central 'ribosome recruitment core' (aa ~642-1091) sufficient to drive translation when tethered to mRNA (PMID:10469664). Through coupled folding, EIF4G1 wraps around the eIF4E N-terminus as a helical 'molecular bracelet' that allosterically enhances cap binding (PMID:14675538), and auxiliary sequences beyond the canonical 4E-binding motif engage the lateral eIF4E surface in a mode that explains competitive displacement by 4E-BPs (PMID:27773676). The central HEAT domain clamps eIF4A in a productive closed conformation, stimulating its RNA-dependent ATPase and helicase activity ~40-fold (PMID:18606994, PMID:16166382, PMID:15528191), with one eIF4A bound per eIF4G despite two contact sites (PMID:11408474). An extended N-terminal segment binds PABP via the RRM2 domain in a poly(A)-regulated manner, coupling the poly(A) tail to translation (PMID:9857202, PMID:23041282), while distinct central subdomains contact eIF3 through the eIF3c/d/e subunits to recruit the 40S subunit (PMID:16766523, PMID:24092755). EIF4G1 additionally provides the docking site that recruits Mnk1 to phosphorylate eIF4E (PMID:7665619) and partitions between mutually exclusive eIF4E and eIF1 complexes that control scanning behavior and start-codon selection (PMID:29987188). Its activity is gated by phosphorylation — Pak2 at Ser896 blocking eIF4E association (PMID:16281055), Cdk1:cyclin B at Ser1232 reprogramming eIF4A and RNA contacts during mitosis (PMID:24248602), and PKCα at Ser1186 modulating Mnk1 interaction (PMID:21576361) — and by O-GlcNAcylation at Ser-61 that controls protein stability (PMID:31300553). EIF4G1 is a hub for translational repression and viral hijacking, being sequestered by Hsp27 during heat shock (PMID:10859165), targeted by repressors such as Musashi1 and Scd6 that compete for PABP or eIF4G (PMID:18490513, PMID:22284680), used by picornaviral, rotaviral, and adenoviral factors to redirect initiation (PMID:10913184, PMID:12086624, PMID:15314025), and cleaved by caspases during Fas-induced apoptosis (PMID:9821956). Neuronal microexon splicing in its prion-like domain acts as a translational brake promoting ribosome stalling and FMRP granule formation (PMID:31999954), and disease-associated familial Parkinson's mutations (Ala502Val, Arg1205His) disrupt eIF4E or eIF3e binding and increase oxidative-stress sensitivity (PMID:21907011).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1995 High

    Established the modular blueprint of eIF4G by mapping which factors bind which region, separating cap-dependent mRNA recruitment from ribosome attachment and helicase functions.

    Evidence Domain-specific proteolysis with rhinovirus 2A and FMDV L proteases plus binding assays in vitro

    PMID:7665619

    Open questions at the time
    • Boundaries are approximate
    • Did not resolve PABP-binding N-terminal extension or PTM control
  2. 1998 High

    Revealed an N-terminal PABP-binding site, connecting the poly(A) tail to translation initiation through eIF4G.

    Evidence 5' RACE ORF extension, co-IP, deletion analysis, and in vitro translation in human/yeast systems

    PMID:9256432 PMID:9857202

    Open questions at the time
    • Structural basis of PABP contact not resolved here
    • Poly(A) allostery not yet defined
  3. 1999 High

    Showed eIF4G is the recruitment platform that brings Mnk1 to phosphorylate eIF4E, and defined a central core sufficient for ribosome recruitment.

    Evidence Co-IP, eIF4E-binding mutants, cell phosphorylation assays, and in vivo tethering of the central domain

    PMID:10469664 PMID:9878069

    Open questions at the time
    • Mnk1 release dynamics undefined
    • C-terminal regulatory function not specified
  4. 2000 High

    Demonstrated eIF4G's central region directs cap-independent (IRES) translation and that eIF4A binding boosts IRES affinity, while heat shock and viral proteases can sequester or destroy eIF4G to shut translation down.

    Evidence In vitro 48S reconstitution on EMCV IRES, purified-protein Hsp27 binding, and FMDV 3C protease cleavage in cells

    PMID:10590115 PMID:10859165 PMID:10913184 PMID:10996799

    Open questions at the time
    • IRES recruitment mechanism partly inferred
    • Hsp27 binding site on eIF4G not mapped
  5. 2003 High

    Resolved that eIF4G undergoes coupled folding around eIF4E as a molecular bracelet that allosterically enhances cap binding, and identified intrinsic RNA-binding sites in eIF4G.

    Evidence NMR solution structure of eIF4E/eIF4G complex with yeast polysome validation; RNA-binding/mutagenesis assays

    PMID:12810920 PMID:12861028 PMID:14675538

    Open questions at the time
    • Allosteric coupling to downstream steps not fully traced
    • Start-codon fidelity role shown in yeast only
  6. 2005 High

    Defined the structural mechanism by which eIF4G stimulates eIF4A — a soft clamp stabilizing the closed helicase conformation — and identified Pak2 as a kinase that inhibits eIF4E association.

    Evidence NMR mapping of the eIF4G middle domain on eIF4A; in vitro kinase assay and Ser896 mutants in depleted lysate

    PMID:15528191 PMID:16166382 PMID:16281055

    Open questions at the time
    • Cooperativity with RNA/ATP inferred from binding states
    • Pak2 signaling context limited
  7. 2006 Medium

    Identified the eIF3 subunit(s) through which eIF4G recruits the 40S subunit and placed this interaction under mTOR/insulin control.

    Evidence Proteolysis-MS, competitive binding, cell-free translation, and insulin/rapamycin co-IP

    PMID:16541103 PMID:16766523

    Open questions at the time
    • mTOR-eIF3-eIF4G link single lab
    • eIF3e-only model later revised
  8. 2008 High

    Provided atomic detail of the eIF4G-eIF4A interface, pinpointing essential residues (Trp579) for helicase activation, and described a small-molecule disruptor of eIF4E/eIF4G.

    Evidence Crystal structure of eIF4G-m/eIF4A with yeast mutagenesis; 4EGI-1 binding/translation assays

    PMID:17254965 PMID:18606994

    Open questions at the time
    • Human structural confirmation pending at this stage
  9. 2012 Medium

    Established the structural and allosteric basis of poly(A)-regulated PABP recognition and showed eIF4G1 selectively supports survival/DNA-damage-response translation in cancer.

    Evidence 2.0 Å crystal structure with NMR/SAXS/ITC/EMSA; siRNA knockdown with polysome profiling and DNA damage foci assays

    PMID:23041282 PMID:23112151

    Open questions at the time
    • mRNA selectivity determinants undefined
    • Cancer role from single lab
  10. 2013 High

    Refined the eIF3-binding model to multiple subunits/subdomains and identified mitotic Cdk1:cyclin B phosphorylation at Ser1232 that reprograms eIF4A and RNA contacts.

    Evidence Fluorescence anisotropy and cross-linking for eIF3 contacts; in vitro Cdk1 phosphorylation with cellular reconstitution

    PMID:24092755 PMID:24248602

    Open questions at the time
    • Functional consequence of mitotic shift on specific mRNAs not detailed
  11. 2016 High

    Clarified the structural mechanism of 4E-BP-like competitive displacement at eIF4E and linked Scd6 arginine methylation to enhanced eIF4G1 repression.

    Evidence Crystal structures of human/Drosophila eIF4E-eIF4G; methylation and pulldown assays in yeast

    PMID:27613419 PMID:27773676

    Open questions at the time
    • Repressor regulation characterized in yeast only
  12. 2018 Medium

    Defined two mutually exclusive eIF4G1 complexes (eIF4E vs eIF1) that determine scanning behavior and start-codon selection.

    Evidence Co-IP, eIF1-binding-deficient mutants, and luciferase reporters

    PMID:29987188

    Open questions at the time
    • Single lab
    • Switch between complexes mechanistically open
  13. 2020 Medium

    Uncovered intrinsic G-quadruplex binding by eIF4G mediating tiRNA repression, and showed a neuronal microexon in the prion-like domain acts as a translational brake driving stalling and FMRP granules.

    Evidence Direct G4 binding/scanning assays; CRISPR microexon deletion with ribosome profiling and mouse behavioral/synaptic assays

    PMID:31999954 PMID:32374873

    Open questions at the time
    • G4-binding region on eIF4G not mapped
    • Microexon mechanism of stalling partly inferred

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many PTMs, alternative complexes, and condensate-promoting domains are integrated to select specific mRNAs for translation in distinct physiological and disease states remains unresolved.
  • No unified model linking PTM combinations to mRNA-specific output
  • Mechanism of Parkinson's-associated dysfunction in vivo unresolved
  • Prion-like domain condensate regulation incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4 GO:0003723 RNA binding 3 GO:0045182 translation regulator activity 3
Localization
GO:0005829 cytosol 3 GO:0005840 ribosome 3
Pathway
R-HSA-392499 Metabolism of proteins 3 R-HSA-8953854 Metabolism of RNA 2
Partners
EIF1EIF3CEIF3EEIF4A1EIF4EHSPB1MKNK1PABPC1
Complex memberships
eIF4F

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 eIF4G recruits Mnk1 to phosphorylate eIF4E: Mnk1 is associated with the eIF4F complex via interaction with the C-terminal region of eIF4G. An eIF4E mutant lacking eIF4G-binding capability shows severely impaired phosphorylation in cells, demonstrating that eIF4G provides a docking site for Mnk1 to phosphorylate eIF4E. Co-immunoprecipitation, in vitro binding assays, cell-based phosphorylation assays with eIF4E mutants The EMBO journal High 9878069
1995 Functional domain mapping of eIF4G by picornaviral proteases: the N-terminal fragment (cpN, containing residues ~319-479) binds eIF4E; the C-terminal fragment (cpC) binds eIF3 (~480-886) and eIF4A (~887-1402). Cleavage separates cap-dependent mRNA recruitment from ribosome attachment/helicase functions. Proteolytic cleavage with rhinovirus 2A and FMDV L proteases, m7GTP-Sepharose chromatography, ultracentrifugal co-sedimentation The Journal of biological chemistry High 7665619
1998 Human eIF4GI contains an N-terminal extension (156 amino acids beyond the previously known sequence) harboring a 29-amino acid PABP-binding site. Full-length eIF4GI (and eIF4GII) binds PABP via RRM1-RRM2 of PABP. An N-terminal fragment including this site inhibits poly(A)-dependent translation in vitro without affecting deadenylated mRNA translation. 5' RACE to extend ORF, co-immunoprecipitation, deletion analysis, in vitro translation assay The EMBO journal High 9857202
2003 Solution NMR structure of yeast eIF4E/cap–eIF4G(393-490) complex: eIF4G(393-490) undergoes coupled folding upon binding, forming a right-handed helical ring (molecular bracelet) around the eIF4E N-terminus. This cofolding allosterically enhances eIF4E cap association and is required for optimal growth and polysome distributions in vivo. NMR solution structure, in vitro binding assays, yeast genetics (growth and polysome analysis) Cell High 14675538
2007 Small-molecule 4EGI-1 binds eIF4E and disrupts eIF4E/eIF4G association, inhibiting cap-dependent translation but not initiation factor-independent translation. Paradoxically, 4EGI-1 enhances 4E-BP1 association with eIF4E both in vitro and in cells. High-throughput screening, in vitro binding assays, cell-based translation assays, co-immunoprecipitation Cell High 17254965
2008 Crystal structure of yeast eIF4G middle domain bound to full-length eIF4A at 2.6 Å: eIF4A adopts an extended conformation where eIF4G holds the DEAD-box motifs in a productive conformation, explaining stimulation of eIF4A helicase activity. eIF4G Trp-579 is essential: Trp579Ala mutation decreases eIF4A binding and causes temperature-sensitive growth in yeast. X-ray crystallography (2.6 Å), site-directed mutagenesis, yeast genetics Proceedings of the National Academy of Sciences of the United States of America High 18606994
2005 NMR spectroscopy mapping of eIF4G middle domain (aa 745-1003) interaction with eIF4A: the main binding surface is on the C-terminal domain of eIF4A. eIF4G-m forms a 'soft clamp' to stabilize the closed interdomain orientation of eIF4A, explaining cooperative stimulation of eIF4A activity together with RNA and ATP. NMR spectroscopy, interface mutagenesis (mutations of interface residues abrogated binding), binding assays Genes & development High 16166382
2016 Crystal structures of human and Drosophila eIF4E–eIF4G complexes reveal that eIF4G auxiliary sequences beyond the canonical 4E-binding motif bind the lateral surface of eIF4E, using a similar mode to that of 4E-BPs, providing a molecular model of competitive displacement. X-ray crystallography (human and Drosophila eIF4E–eIF4G complexes) Molecular cell High 27773676
2012 Crystal structure at 2.0 Å of poly(A)11·PABP(1-190)·eIF4G(178-203) ternary complex: eIF4G interacts with the RRM2 domain of PABP, and this interaction is allosterically regulated by poly(A) binding to PABP (interdomain allostery). Confirmed by NMR, SAXS, ITC, EMSA, and immunoprecipitation from HeLa extracts. X-ray crystallography (2.0 Å), NMR, SAXS, ITC, EMSA, co-immunoprecipitation from HeLa cells Molecular cell High 23041282
2006 Human eIF4G-1 binds eIF3 through the eIF3e (p48/Int-6) subunit. Recombinant FLAG-eIF3e competes with native eIF3 for binding to the eIF3-binding domain of eIF4G-1 in vitro. Addition of FLAG-eIF3e to cell-free translation inhibits cap-dependent translation and causes loss of eIF4G from 40S complexes. Partial proteolysis of eIF3 followed by mass spectrometry, competitive binding assay, cell-free translation assay, polysome analysis The Journal of biological chemistry High 16766523
2013 eIF4G binds eIF3 through subunits eIF3c, eIF3d, and eIF3e (not only eIF3e), with two distinct eIF3-binding subdomains in eIF4G. Both subdomains are required for efficient mRNA recruitment and translation. eIF4G binding to eIF3 is independent of eIF4A binding to the eIF4G middle region. Fluorescence anisotropy, site-specific cross-linking, eIF4G-dependent translation assay The Journal of biological chemistry High 24092755
2006 mTOR controls the association of eIF3 and eIF4G in response to insulin: insulin increased eIF4G bound to eIF3 up to fivefold; this was blocked by rapamycin and did not require eIF4E binding to eIF4G or eIF3 binding to 40S. mTOR was found to interact directly with eIF3. Co-immunoprecipitation, pharmacological inhibition (rapamycin), insulin stimulation in cells The EMBO journal Medium 16541103
2000 Hsp27 specifically binds eIF4G during heat shock, preventing assembly of the eIF4F cap-initiation complex and trapping eIF4G in insoluble heat shock granules. Purified Hsp27 bound purified eIF4G in vitro, prevented in vitro translation, and promoted eIF4G insolubilization. eIF4E, eIF4A, Mnk1, PABP, eIF4B, and eIF3 were not bound by Hsp27. Co-immunoprecipitation, in vitro binding with purified proteins, in vitro translation assay, cell fractionation, overexpression studies Genes & development High 10859165
2000 The central region of eIF4GI (aa 613-1090) mediates EMCV IRES-dependent translation; the IRES-binding fragment maps to aa 746-949. Physical association of eIF4GI with eIF4A increases eIF4GI affinity for the EMCV IRES by ~100-fold but not for beta-globin mRNA. eIF4GI mutants defective in eIF4A binding fail to support 48S complex formation on the IRES even if they bind the IRES normally. Mutational analysis, RNA binding assays in vitro, 48S complex formation assay in vitro Molecular and cellular biology High 10913184
1999 The conserved central domain (aa 642-1091) of human eIF4GI, lacking eIF4E- and PABP-binding sites, functions as an autonomous 'ribosome recruitment core' sufficient to drive translation in vivo when tethered to an mRNA via IRP-1 fusion. The C-terminal third is dispensable and may serve as a regulatory domain. Chimeric protein tethering assay in vivo, deletion analysis The EMBO journal Medium 10469664
2000 FMDV 3C protease cleaves both eIF4G and eIF4A within infected cells; the 3C-generated eIF4G cleavage products differ from those produced by the L protease. Demonstrated by transient expression of 3C protease. Transient expression assay, Western blotting of infected and transfected cells Journal of virology Medium 10590115
1996 The eIF4G-eIF4E complex (eIF4F) is the preferred substrate for rhinovirus 2A protease cleavage: eIF4G alone is a poor substrate, but the eIF4G-eIF4E complex is cleaved efficiently. An eIF4G-eIF4E complex (but not eIF4G alone) was required to restore translation of capped mRNA. In vitro cleavage assay with purified recombinant proteins, in vitro translation reconstitution assay Journal of virology High 8970966
2002 X-ray structure of rotavirus NSP3 C-terminal domain (NSP3-C) in complex with a fragment of eIF4GI: homodimerization of NSP3-C forms two hydrophobic eIF4G-binding pockets at the dimer interface. NSP3 and PABP use analogous eIF4G recognition strategies. Site-directed mutagenesis and ITC validated the binding mechanism. X-ray crystallography, site-directed mutagenesis, isothermal titration calorimetry Molecular cell High 12086624
2004 eIF4G is required for the pioneer round of translation in mammalian cells: CBP80 and CBP20 independently interact with eIF4GI; cleavage of eIF4G by HIV-2 or poliovirus 2A protease inhibits nonsense-mediated mRNA decay. eIF4GI co-immunopurifies with pre-mRNA and with NMD factors Upf proteins and eIF4AIII. Co-immunoprecipitation (baculovirus-produced CBP80/CBP20 with eIF4GI), viral protease-mediated cleavage, NMD reporter assay Nature structural & molecular biology Medium 15361857
2004 The eIF4G central domain (cpC3, aa ~480-886) stimulates RNA-dependent ATPase activity of eIF4A ~40-fold by lowering Km(RNA) 10-fold and raising kcat 4-fold; it interacts with the N-terminal domain of eIF4A. The C-terminal eIF4A-binding domain (cpC2) does not stimulate ATPase activity. In vitro ATPase assay with purified recombinant domains, RNA cross-linking, kinetic analysis The Journal of biological chemistry High 15528191
2011 eIF4G1 mutations p.Ala502Val and p.Arg1205His (associated with familial Parkinson's disease) disrupt eIF4E or eIF3e binding respectively, while wild-type eIF4G1 does not show this disruption. Mutant cells are more vulnerable to reactive oxidative species. Co-immunoprecipitation, ROS sensitivity assay, genetic segregation analysis American journal of human genetics Medium 21907011
2011 PKCα phosphorylates eIF4G1 at Ser1186. PKCα activation via phorbol esters elicits orchestrated phosphorylation events that modulate eIF4G1 structure and control interaction with the eIF4E kinase Mnk1. Phosphoproteomics, site-directed mutagenesis, PKCα-specific activation with phorbol esters Molecular and cellular biology Medium 21576361
2010 MAPK-mediated phosphorylation of the Mnk1 active site controls eIF4G binding: the C-terminal domain of Mnk1 restricts its eIF4G interaction. Mnk1 autoregulates its interaction with eIF4G, releasing itself after phosphorylating its substrate (eIF4E). This was demonstrated using a splice variant, kinase-dead mutant, and small-molecule Mnk1 inhibitor. Co-immunoprecipitation, splice variant analysis, kinase-dead mutant, Mnk1 inhibitor Molecular and cellular biology Medium 20823271
2013 Cdk1:cyclin B phosphorylates eIF4G1 at Ser1232 during mitosis. This phosphorylation strongly enhances eIF4A interaction with HEAT domain 2 of eIF4G but decreases association of the eIF4G/eIF4A complex with RNA, implicating this event in the mitotic translation initiation shift. Phosphoproteomics, in vitro phosphorylation with recombinant Cdk1:cyclin B, kinase inhibition assays, kinase depletion-reconstitution, co-immunoprecipitation Molecular and cellular biology High 24248602
2005 Pak2 binds to and phosphorylates eIF4G at Ser896, inhibiting association of eIF4E with the m7GTP cap and reducing translation initiation. Pak2 and eIF4E compete for binding to this site on eIF4G. The S896D phosphomimetic mutant inhibits translation while S896A does not. In vitro kinase assay, eIF4G-depleted reticulocyte lysate reconstitution, eIF4G Ser896 mutants, RNA interference The EMBO journal High 16281055
2008 Neural RNA-binding protein Musashi1 (Msi1) inhibits translation initiation by competing with eIF4G for binding to PABP. This competition prevents assembly of the 80S ribosome (but not the 48S complex). Deletion of the PABP-interacting domain in Msi1 abolishes its translational repression function. Identification of PABP as Msi1-binding partner, competitive binding assay with eIF4G, ribosome assembly assay, deletion mutant analysis, stress granule localization The Journal of cell biology Medium 18490513
2000 eIF4G-PABP interaction is critical for translational control in Xenopus oocytes: expression of an eIF4GI mutant defective in PABP binding reduces translation of polyadenylated mRNA and dramatically inhibits progesterone-induced oocyte maturation. Microinjection of mutant eIF4GI into Xenopus oocytes, in vivo translation assay, maturation assay Current biology : CB Medium 10996799
2004 Adenovirus 100K protein possesses a selective binding element for the tripartite leader mRNA, forms a complex with eIF4G and PABP, and promotes ribosome shunting. The ability of 100K to bind both the tripartite leader and eIF4G is critical for ribosome shunting. 100K competitively displaces Mnk1 from eIF4G and blocks eIF4E phosphorylation. Co-immunoprecipitation, polysome analysis, mutational analysis, in vitro translation assay Genes & development Medium 15314025
2004 Adenovirus 100K protein displaces Mnk1 from eIF4G via a shared eIF4G-binding motif located in the N-terminal 66 aa of 100K. 100K binds eIF4G more strongly than Mnk1 and its binding is RNA-independent, unlike Mnk1 whose eIF4G binding is RNA-dependent. Co-immunoprecipitation, competitive binding assay, domain mapping, in vitro translation assay Journal of virology Medium 15220445
1997 Yeast eIF4G homologs (Tif4631p and Tif4632p) share a conserved Pab1p-binding site required for poly(A)-tail-stimulated translation of uncapped mRNAs in vitro and for synergistic cap/poly(A) stimulation. The region encompassing the Pab1p-binding site on eIF4G1 becomes essential for growth when the eIF4E-binding site is mutated. In vitro translation assay, deletion/mutation analysis, yeast genetic epistasis Proceedings of the National Academy of Sciences of the United States of America High 9256432
2012 Scd6 (yeast) represses translation by binding the eIF4G subunit of eIF4F via its RGG domain, forming a translation-repressed mRNP. Several other RGG-domain proteins (Npl3, Sbp1) also directly bind eIF4G and repress translation via their RGG motifs. Co-purification, direct binding assay, in vivo translation repression assay Molecular cell Medium 22284680
2003 Yeast eIF4G1 binds single-stranded RNA at three distinct sites: N-terminal (aa 1-82), middle (aa 492-539, RS-rich), and C-terminal (aa 883-952, RS-rich). Full-length eIF4G1 has ~100-fold higher RNA affinity than individual sites alone. Deletion of any two sites strongly impairs in vitro translation and yeast cell growth; arginine-to-alanine mutations in the middle RS site abolish its RNA-binding activity. RNA binding assay, alanine mutagenesis, in vitro translation, yeast growth assay RNA (New York, N.Y.) Medium 12810920
2020 eIF4G has intrinsic G-quadruplex (G4) binding activity that is required for tiRNA-mediated translation repression. Targeting eIF4G with G4-forming tiRNAs impairs 40S ribosome scanning on mRNAs and leads to formation of eIF2α-independent stress granules. Direct binding assay (G4-eIF4G), ribosome scanning assay, stress granule imaging, tiRNA functional assays Nucleic acids research Medium 32374873
2020 Neuronal microexons in eIF4G1 (and eIF4G3) overlapping prion-like domains are activity-dependent in their splicing and frequently disrupted in autism. CRISPR-Cas9 deletion of the eIF4G1 microexon selectively upregulates synaptic proteins, causes ribosome stalling, and promotes coalescence of cytoplasmic granule components including FMRP. Mice lacking the Eif4g1 microexon show social behavior, learning, and memory deficits with altered hippocampal synaptic plasticity. CRISPR-Cas9 deletion, ribosome profiling, RNA-seq, mouse behavioral assays, synaptic plasticity electrophysiology, granule imaging Molecular cell High 31999954
2012 eIF4G1 upregulation in breast cancer cells selectively increases translation of mRNAs involved in survival and DNA damage response following ionizing radiation. Reduced eIF4G1 (but not eIF4G2) sensitizes cells to DNA damage and delays resolution of DNA damage foci with little effect on overall protein synthesis, establishing a specific role for eIF4G1 in specialized translation. siRNA knockdown, polysome profiling, translation reporter assays, DNA damage foci assay, apoptosis and autophagy assays Proceedings of the National Academy of Sciences of the United States of America Medium 23112151
2003 Yeast eIF4G2 HEAT domain and flanking residues are required for optimal interaction with AUG recognition factors eIF5 and eIF1. eIF1 binds simultaneously to eIF4G and eIF3c in vitro. HEAT domain mutations that impair eIF4G–eIF1/eIF5 interaction enhance translation from a non-AUG codon, indicating a role in start-codon fidelity. In vitro binding assay, genetic co-overexpression suppression, start-codon fidelity reporter Molecular and cellular biology Medium 12861028
2018 eIF4G1 exists in two mutually exclusive complexes: one with eIF4E and one with eIF1. The eIF1-eIF4G1 interaction promotes leaky scanning and prevents cap-proximal initiation, while eIF4E-eIF4G1 antagonizes scanning and is required for TISU-dependent translation. The eIF1-binding site on eIF4G1 is also indirectly contacted by eIF4E. Co-immunoprecipitation, eIF1 binding-deficient mutant, luciferase translation reporters, domain mapping Molecular and cellular biology Medium 29987188
2019 OGT O-GlcNAc-modifies eIF4G1 at Ser-61, and this modification is critical for eIF4G1 protein stability. Loss of OGT in β-cells reduces eIF4G1 stability, leading to decreased CPE levels and impaired proinsulin processing. Overexpression of eIF4G1 in βOGTKO islets fully reverses hyperproinsulinemia. Click O-GlcNAc labeling, site-directed mutagenesis (Ser-61), immunoblotting, islet overexpression rescue experiments The Journal of biological chemistry Medium 31300553
2016 Arginine methylation of the Scd6 RGG motif by the methyltransferase Hmt1 promotes Scd6 binding to eIF4G1 and augments translation repression activity. An arginine methylation-defective Scd6 mutant fails to bind eIF4G1 efficiently and is defective in stress granule formation. In vivo methylation assay, pulldown binding assay with eIF4G1, live-cell imaging, growth rescue assay Nucleic acids research Medium 27613419
2014 VPS35 and EIF4G1 interact genetically in yeast and converge on α-synuclein pathobiology. EIF4G1 upregulation causes protein misfolding defects; expression of sortilin downstream of VPS35 rescues these defects. These genetic interactions are conserved in worm and mouse neurons. Yeast genetic interaction screen, overexpression/suppression experiments, transgenic mouse model, neuronal models Neuron Medium 25533483
2002 CBP80 (cap-binding protein 80) and eIF4G share a common origin and similar HEAT domain organization. A structural model based on the CBP80-CBP20 crystal structure suggests how the domains of eIF4G are oriented and could interact with translation factors. Sequence and structural analysis, domain homology modeling based on CBP80-CBP20 crystal structure Biochemistry Low 16156639
2001 In human cells, eIF4G is associated with eIF4AI or eIF4AII but not both simultaneously, establishing a 1:1 stoichiometry rather than 1:2. Tagged eIF4A complexes with eIF4G contain no endogenous eIF4A, confirming that each eIF4G binds only one molecule of eIF4A despite having two binding sites. Co-immunoprecipitation of tagged eIF4A isoforms in HEK cells The Journal of biological chemistry Medium 11408474
2004 Leucine stimulates eIF4E·eIF4G assembly and eIF4G(Ser1108) phosphorylation in rat skeletal muscle through a signaling pathway independent of mTOR (unaffected by rapamycin or PI3K inhibition). Hindlimb perfusion model, co-immunoprecipitation (eIF4E IP), Western blotting for phospho-eIF4G(Ser1108) The Journal of nutrition Medium 15226457
1998 Fas/CD95 receptor activation in Jurkat cells induces caspase-dependent cleavage of eIF4G, inhibition of total protein synthesis, and cell death. Caspase inhibitors zVAD.FMK and zDEVD.FMK prevent both eIF4G cleavage and cell death. Signaling through p38 MAP kinase is not required for Fas-induced eIF4G cleavage. Fas receptor activation, caspase inhibitor treatment, Western blot for eIF4G cleavage, protein synthesis measurement FEBS letters Medium 9821956

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to phosphorylate eIF4E. The EMBO journal 539 9878069
1995 Mapping of functional domains in eukaryotic protein synthesis initiation factor 4G (eIF4G) with picornaviral proteases. Implications for cap-dependent and cap-independent translational initiation. The Journal of biological chemistry 500 7665619
1998 A newly identified N-terminal amino acid sequence of human eIF4G binds poly(A)-binding protein and functions in poly(A)-dependent translation. The EMBO journal 488 9857202
2007 Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Cell 473 17254965
1998 Interaction of polyadenylate-binding protein with the eIF4G homologue PAIP enhances translation. Nature 320 9548260
2003 Ribosome loading onto the mRNA cap is driven by conformational coupling between eIF4G and eIF4E. Cell 295 14675538
1997 Translation initiation factor eIF4G mediates in vitro poly(A) tail-dependent translation. Proceedings of the National Academy of Sciences of the United States of America 272 9256432
2011 Translation initiator EIF4G1 mutations in familial Parkinson disease. American journal of human genetics 216 21907011
2008 Crystal structure of the yeast eIF4A-eIF4G complex: an RNA-helicase controlled by protein-protein interactions. Proceedings of the National Academy of Sciences of the United States of America 203 18606994
2003 Conducting the initiation of protein synthesis: the role of eIF4G. Biology of the cell 189 12867079
2008 Neural RNA-binding protein Musashi1 inhibits translation initiation by competing with eIF4G for PABP. The Journal of cell biology 172 18490513
2000 Physical association of eukaryotic initiation factor 4G (eIF4G) with eIF4A strongly enhances binding of eIF4G to the internal ribosomal entry site of encephalomyocarditis virus and is required for internal initiation of translation. Molecular and cellular biology 167 10913184
2000 Foot-and-mouth disease virus 3C protease induces cleavage of translation initiation factors eIF4A and eIF4G within infected cells. Journal of virology 160 10590115
2000 Chaperone hsp27 inhibits translation during heat shock by binding eIF4G and facilitating dissociation of cap-initiation complexes. Genes & development 153 10859165
2006 Translation initiation factor eIF4G-1 binds to eIF3 through the eIF3e subunit. The Journal of biological chemistry 144 16766523
2014 Parkinson's disease genes VPS35 and EIF4G1 interact genetically and converge on α-synuclein. Neuron 143 25533483
1999 Translation driven by an eIF4G core domain in vivo. The EMBO journal 141 10469664
2007 Accumulation of polyadenylated mRNA, Pab1p, eIF4E, and eIF4G with P-bodies in Saccharomyces cerevisiae. Molecular biology of the cell 137 17475768
2013 Human eukaryotic initiation factor 4G (eIF4G) protein binds to eIF3c, -d, and -e to promote mRNA recruitment to the ribosome. The Journal of biological chemistry 134 24092755
2005 Structural basis for the enhancement of eIF4A helicase activity by eIF4G. Genes & development 129 16166382
1998 Cooperative modulation by eIF4G of eIF4E-binding to the mRNA 5' cap in yeast involves a site partially shared by p20. The EMBO journal 127 9707439
1996 The eIF4G-eIF4E complex is the target for direct cleavage by the rhinovirus 2A proteinase. Journal of virology 123 8970966
2000 Interaction of the eIF4G initiation factor with the aphthovirus IRES is essential for internal translation initiation in vivo. RNA (New York, N.Y.) 119 11073214
2010 Regulation of eukaryotic initiation factor 4E (eIF4E) phosphorylation by mitogen-activated protein kinase occurs through modulation of Mnk1-eIF4G interaction. Molecular and cellular biology 113 20823271
2001 eIF4G functionally differs from eIFiso4G in promoting internal initiation, cap-independent translation, and translation of structured mRNAs. The Journal of biological chemistry 112 11483601
2016 The Structures of eIF4E-eIF4G Complexes Reveal an Extended Interface to Regulate Translation Initiation. Molecular cell 110 27773676
2012 Interdomain allostery promotes assembly of the poly(A) mRNA complex with PABP and eIF4G. Molecular cell 110 23041282
2002 Recognition of eIF4G by rotavirus NSP3 reveals a basis for mRNA circularization. Molecular cell 108 12086624
2012 Scd6 targets eIF4G to repress translation: RGG motif proteins as a class of eIF4G-binding proteins. Molecular cell 107 22284680
2006 mTOR-dependent stimulation of the association of eIF4G and eIF3 by insulin. The EMBO journal 107 16541103
2004 Leucine regulates translation initiation in rat skeletal muscle via enhanced eIF4G phosphorylation. The Journal of nutrition 105 15226457
2000 Interaction of eIF4G with poly(A)-binding protein stimulates translation and is critical for Xenopus oocyte maturation. Current biology : CB 103 10996799
2011 Blocking eIF4E-eIF4G interaction as a strategy to impair coronavirus replication. Journal of virology 99 21507972
2020 Autism-Misregulated eIF4G Microexons Control Synaptic Translation and Higher Order Cognitive Functions. Molecular cell 97 31999954
2012 DNA damage and eIF4G1 in breast cancer cells reprogram translation for survival and DNA repair mRNAs. Proceedings of the National Academy of Sciences of the United States of America 92 23112151
2007 Frequent overexpression of the genes FXR1, CLAPM1 and EIF4G located on amplicon 3q26-27 in squamous cell carcinoma of the lung. International journal of cancer 92 17290396
2020 eIF4G has intrinsic G-quadruplex binding activity that is required for tiRNA function. Nucleic acids research 90 32374873
2003 The yeast eukaryotic initiation factor 4G (eIF4G) HEAT domain interacts with eIF1 and eIF5 and is involved in stringent AUG selection. Molecular and cellular biology 86 12861028
2014 eIF4B, eIF4G and RNA regulate eIF4A activity in translation initiation by modulating the eIF4A conformational cycle. Nucleic acids research 82 24848014
2010 The eIF4E/eIF4G interaction inhibitor 4EGI-1 augments TRAIL-mediated apoptosis through c-FLIP Down-regulation and DR5 induction independent of inhibition of cap-dependent protein translation. Neoplasia (New York, N.Y.) 81 20360945
2004 eIF4G is required for the pioneer round of translation in mammalian cells. Nature structural & molecular biology 81 15361857
2006 The potyviral virus genome-linked protein VPg forms a ternary complex with the eukaryotic initiation factors eIF4E and eIF4G and reduces eIF4E affinity for a mRNA cap analogue. The FEBS journal 80 16519694
2010 Multiple elements in the eIF4G1 N-terminus promote assembly of eIF4G1•PABP mRNPs in vivo. The EMBO journal 79 21139564
2008 Nuclear localization of cytoplasmic poly(A)-binding protein upon rotavirus infection involves the interaction of NSP3 with eIF4G and RoXaN. Journal of virology 78 18799579
2017 Reducing eIF4E-eIF4G interactions restores the balance between protein synthesis and actin dynamics in fragile X syndrome model mice. Science signaling 76 29114037
2010 Polypyrimidine tract-binding protein stimulates the poliovirus IRES by modulating eIF4G binding. The EMBO journal 72 20859255
2004 Tethering of eIF4G to adenoviral mRNAs by viral 100k protein drives ribosome shunting. Genes & development 67 15314025
2002 The histone 3'-terminal stem-loop-binding protein enhances translation through a functional and physical interaction with eukaryotic initiation factor 4G (eIF4G) and eIF3. Molecular and cellular biology 63 12391154
2013 eIF4B and eIF4G jointly stimulate eIF4A ATPase and unwinding activities by modulation of the eIF4A conformational cycle. Journal of molecular biology 62 24080224
2010 Synergistic activation of eIF4A by eIF4B and eIF4G. Nucleic acids research 62 21113024
2002 Overexpression of the eukaryotic translation initiation factor 4G (eIF4G-1) in squamous cell lung carcinoma. International journal of cancer 62 11857405
2003 RNA-binding activity of translation initiation factor eIF4G1 from Saccharomyces cerevisiae. RNA (New York, N.Y.) 61 12810920
2004 Interaction between the NH2-terminal domain of eIF4A and the central domain of eIF4G modulates RNA-stimulated ATPase activity. The Journal of biological chemistry 60 15528191
1998 Cleavage of translation initiation factor 4G (eIF4G) during anti-Fas IgM-induced apoptosis does not require signalling through the p38 mitogen-activated protein (MAP) kinase. FEBS letters 60 9821956
2011 Phosphorylation of eukaryotic translation initiation factor 4G1 (eIF4G1) by protein kinase C{alpha} regulates eIF4G1 binding to Mnk1. Molecular and cellular biology 56 21576361
2006 Functional analysis of individual binding activities of the scaffold protein eIF4G. The Journal of biological chemistry 56 17130132
2011 Depletion of eIF4G from yeast cells narrows the range of translational efficiencies genome-wide. BMC genomics 55 21269496
2005 Inhibition of cap-dependent translation via phosphorylation of eIF4G by protein kinase Pak2. The EMBO journal 54 16281055
2013 Whole exome sequencing of rare variants in EIF4G1 and VPS35 in Parkinson disease. Neurology 53 23408866
2011 Human eIF4AIII interacts with an eIF4G-like partner, NOM1, revealing an evolutionarily conserved function outside the exon junction complex. Genes & development 52 21576267
2016 An accurately preorganized IRES RNA structure enables eIF4G capture for initiation of viral translation. Nature structural & molecular biology 51 27525590
2010 Functional overlap between eIF4G isoforms in Saccharomyces cerevisiae. PloS one 50 20161741
2005 eIF4G and CBP80 share a common origin and similar domain organization: implications for the structure and function of eIF4G. Biochemistry 49 16156639
1999 Interaction of translation initiation factor eIF4G with eIF4A in the yeast Saccharomyces cerevisiae. The Journal of biological chemistry 49 10480875
2004 Structural basis for competitive inhibition of eIF4G-Mnk1 interaction by the adenovirus 100-kilodalton protein. Journal of virology 46 15220445
2004 Cleavage of eukaryotic initiation factor eIF4G and inhibition of host-cell protein synthesis during feline calicivirus infection. The Journal of general virology 42 15105529
2002 Mass spectrometric analysis of the N terminus of translational initiation factor eIF4G-1 reveals novel isoforms. The Journal of biological chemistry 39 11821405
1997 cDNA cloning, expression analysis, and chromosomal localization of a gene with high homology to wheat eIF-(iso)4F and mammalian eIF-4G. Genomics 39 9027506
2018 Metformin blocks MYC protein synthesis in colorectal cancer via mTOR-4EBP-eIF4E and MNK1-eIF4G-eIF4E signaling. Molecular oncology 38 30221473
2014 Insulin regulates carboxypeptidase E by modulating translation initiation scaffolding protein eIF4G1 in pancreatic β cells. Proceedings of the National Academy of Sciences of the United States of America 38 24843127
2012 MNK2 inhibits eIF4G activation through a pathway involving serine-arginine-rich protein kinase in skeletal muscle. Science signaling 38 22337810
2007 A novel eIF4G homolog, Off-schedule, couples translational control to meiosis and differentiation in Drosophila spermatocytes. Development (Cambridge, England) 38 17611222
2018 Structural motifs in eIF4G and 4E-BPs modulate their binding to eIF4E to regulate translation initiation in yeast. Nucleic acids research 37 30053226
2017 Eukaryotic translation initiation factor 4G (eIF4G) coordinates interactions with eIF4A, eIF4B, and eIF4E in binding and translation of the barley yellow dwarf virus 3' cap-independent translation element (BTE). The Journal of biological chemistry 36 28242763
2015 The EIF4G1 gene and Parkinson's disease. Acta neurologica Scandinavica 36 25765080
2013 Mitotic phosphorylation of eukaryotic initiation factor 4G1 (eIF4G1) at Ser1232 by Cdk1:cyclin B inhibits eIF4A helicase complex binding with RNA. Molecular and cellular biology 36 24248602
2008 Kinetic mechanism for assembly of the m7GpppG.eIF4E.eIF4G complex. The Journal of biological chemistry 36 18614538
2007 eIF4G, eIFiso4G, and eIF4B bind the poly(A)-binding protein through overlapping sites within the RNA recognition motif domains. The Journal of biological chemistry 36 17606619
2016 Arginine methylation promotes translation repression activity of eIF4G-binding protein, Scd6. Nucleic acids research 35 27613419
2001 Eukaryotic initiation factors 4A (eIF4A) and 4G (eIF4G) mutually interact in a 1:1 ratio in vivo. The Journal of biological chemistry 35 11408474
2004 Phosphorylation of Mnk1 by caspase-activated Pak2/gamma-PAK inhibits phosphorylation and interaction of eIF4G with Mnk. The Journal of biological chemistry 34 15234964
2013 Molecular crowding enhanced ATPase activity of the RNA helicase eIF4A correlates with compaction of its quaternary structure and association with eIF4G. Journal of the American Chemical Society 33 23767688
2018 Eukaryotic Translation Initiation Factor 4 Gamma 1 (eIF4G1) is upregulated during Prostate cancer progression and modulates cell growth and metastasis. Scientific reports 32 29748619
2017 Viral and cellular mRNA-specific activators harness PABP and eIF4G to promote translation initiation downstream of cap binding. Proceedings of the National Academy of Sciences of the United States of America 32 28559344
2015 Two related trypanosomatid eIF4G homologues have functional differences compatible with distinct roles during translation initiation. RNA biology 31 25826663
2012 Sequential eukaryotic translation initiation factor 5 (eIF5) binding to the charged disordered segments of eIF4G and eIF2β stabilizes the 48S preinitiation complex and promotes its shift to the initiation mode. Molecular and cellular biology 31 22851688
2007 Perillyl alcohol and genistein differentially regulate PKB/Akt and 4E-BP1 phosphorylation as well as eIF4E/eIF4G interactions in human tumor cells. Archives of biochemistry and biophysics 31 17601486
2012 Study of the genetic variability in a Parkinson's Disease gene: EIF4G1. Neuroscience letters 30 22561553
2012 EIF4G1 in familial Parkinson's disease: pathogenic mutations or rare benign variants? Neurobiology of aging 30 22658323
2019 Eukaryotic Translation Initiation Factor 4 Gamma 1 (EIF4G1): a target for cancer therapeutic intervention? Cancer cell international 29 31496918
2017 Translation initiation factor eIF4G1 preferentially binds yeast transcript leaders containing conserved oligo-uridine motifs. RNA (New York, N.Y.) 29 28546148
2020 RNA-tethering assay and eIF4G:eIF4A obligate dimer design uncovers multiple eIF4F functional complexes. Nucleic acids research 28 32749456
2018 Dynamic Interaction of Eukaryotic Initiation Factor 4G1 (eIF4G1) with eIF4E and eIF1 Underlies Scanning-Dependent and -Independent Translation. Molecular and cellular biology 28 29987188
2013 EIF4G1 Ala502Val and Arg1205His variants in Chinese patients with Parkinson disease. Neuroscience letters 28 23562511
2016 Functional role of eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) in NSCLC. Oncotarget 27 27003362
2011 Functional impairment of eIF4A and eIF4G factors correlates with inhibition of influenza virus mRNA translation. Virology 27 21377182
2019 eIF4G1 and carboxypeptidase E axis dysregulation in O-GlcNAc transferase-deficient pancreatic β-cells contributes to hyperproinsulinemia in mice. The Journal of biological chemistry 26 31300553
2012 VPS35 Asp620Asn and EIF4G1 Arg1205His mutations are rare in Parkinson disease from southwest China. Neurobiology of aging 25 23261770
2014 Magnesium-dependent folding of a picornavirus IRES element modulates RNA conformation and eIF4G interaction. The FEBS journal 24 24961997
2013 EIF4G1 R1205H and VPS35 D620N mutations are rare in Parkinson's disease from South Africa. Neurobiology of aging 24 24080171

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