Affinage

EIF4EBP1

Eukaryotic translation initiation factor 4E-binding protein 1 · UniProt Q13541

Length
118 aa
Mass
12.6 kDa
Annotated
2026-06-09
100 papers in source corpus 41 papers cited in narrative 42 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EIF4EBP1 (4E-BP1/PHAS-I) is an intrinsically disordered translational repressor that binds the cap-binding factor eIF4E and blocks cap-dependent translation initiation when hypophosphorylated, releasing eIF4E upon phosphorylation (PMID:7939721, PMID:8599949). Its activity is governed by hierarchical multisite phosphorylation: mTOR (FRAP/RAFT1) directly phosphorylates priming sites Thr-37/Thr-46 even on eIF4E-bound 4E-BP1, which licenses subsequent phosphorylation of the serum-sensitive C-terminal sites Ser-65/Thr-70 that drive eIF4E dissociation (PMID:9204908, PMID:9465032, PMID:10364159); CDK12 carries out the late Ser-65/Thr-70 events on a defined mRNA network downstream of mTORC1 priming (PMID:30819820). Efficient phosphorylation requires bivalent tethering of 4E-BP1 to Raptor through its N-terminal RAIP and C-terminal TOS motifs, which orients the disordered central region toward the mTOR active site and explains both the phosphorylation hierarchy and the differential rapamycin sensitivity of individual sites (PMID:12665511, PMID:12747827, PMID:33852892). Upstream, PI3K–Akt signaling feeds into mTORC1 to inactivate 4E-BP1 (PMID:9472019), while transcriptional regulators set its abundance: FOXO1, Smad4, and ATF4 induce it (PMID:17510058, PMID:19834456, PMID:18316032) and Snail represses it, with low 4E-BP1 conferring resistance to mTOR inhibitors (PMID:29263324). Through these mechanisms 4E-BP1 controls selective translation of growth and survival mRNAs and acts as the key effector mediating cardiomyocyte viability downstream of mTOR loss (PMID:20644257), circadian rhythm entrainment via VIP translation in the SCN (PMID:23972597), and muscle metabolic adaptation through PGC-1α translation (PMID:26121750). Beyond translation, 4E-BP1 has non-canonical roles in mitosis, localizing to centrosomes and the meiotic spindle and being phosphorylated by CDK1 (Ser-83) and PLK1 (PMID:22918237, PMID:27402756, PMID:28272965), and its stability is controlled by O-GlcNAcylation-dependent suppression of CUL3-mediated ubiquitin–proteasome degradation (PMID:30733333).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1994 High

    Established the core mechanism: 4E-BP1 represses translation by binding eIF4E, and phosphorylation relieves this repression, linking a signaling input to cap-dependent translation.

    Evidence In vitro binding with cap-affinity resin and kinase assays in adipocyte extracts; cDNA cloning and biochemical characterization

    PMID:7939721 PMID:8170978

    Open questions at the time
    • Identity of the physiological kinase(s) not resolved (MAP kinase implicated in vitro)
    • No structural basis for eIF4E binding/release
  2. 1996 High

    Placed 4E-BP1 in the rapamycin-sensitive mTOR pathway and showed its dephosphorylation is the mechanistic basis for rapamycin's selective block of cap-dependent translation, distinguishing it from MAP kinase control.

    Evidence Co-IP, in vitro translation comparing cap- vs IRES-driven reporters, rapamycin/wortmannin/MEK inhibitor epistasis across multiple cell types and rat skeletal muscle

    PMID:7638171 PMID:8599949 PMID:8633019 PMID:8779938

    Open questions at the time
    • Did not establish whether mTOR phosphorylates 4E-BP1 directly or via an intermediate kinase
    • Specific sites not mapped
  3. 1997 High

    Demonstrated that mTOR directly phosphorylates 4E-BP1 and does so in parallel to, not downstream of, S6K1, defining 4E-BP1 as a direct mTOR substrate.

    Evidence In vitro kinase assays with mTOR immunoprecipitate; rapamycin-resistant and kinase-dead mTOR mutants in cells

    PMID:9204908 PMID:9334222

    Open questions at the time
    • Site assignment incomplete
    • Did not address requirement for accessory targeting subunits
  4. 1998 High

    Mapped direct mTOR phosphoacceptor sites and positioned the PI3K/Akt pathway upstream of mTOR-dependent 4E-BP1 inactivation.

    Evidence In vitro kinase/phosphopeptide mapping (Thr-36/Thr-45); dominant-negative and constitutively active Akt with wortmannin/rapamycin

    PMID:9465032 PMID:9472019

    Open questions at the time
    • Akt acts via mTOR but the intervening steps were undefined
    • Did not explain multi-site ordering
  5. 1999 High

    Resolved the hierarchical two-step phosphorylation logic — priming at Thr-37/46 enables C-terminal Ser-65/Thr-70 phosphorylation that releases eIF4E — and indicated an mTOR-associated activity contributes to the late sites.

    Evidence In vitro mTOR kinase assays, MS site identification, mutagenesis of Thr-37/46; mTOR-immunoprecipitate fractionation; Akt-isoform specificity in myotubes

    PMID:10364159 PMID:10400692 PMID:10471835

    Open questions at the time
    • Identity of the co-purifying C-terminal kinase not determined
    • Relative contribution of individual sites to release left open
  6. 2003 High

    Defined the Raptor-dependent targeting mechanism, showing RAIP and TOS motifs are both required for efficient mTOR phosphorylation, eIF4E release, and cell size control.

    Evidence In vitro mTOR/Raptor complex kinase assays with RAIP/TOS mutants; Raptor co-IP; in vivo phosphorylation; cell size measurement; mutational dissection of site contributions to eIF4E release

    PMID:12618431 PMID:12665511 PMID:12747827 PMID:14507920

    Open questions at the time
    • Structural geometry of dual-motif tethering not yet resolved
    • Did not explain rapamycin resistance of specific sites
  7. 2008 High

    Clarified that 4E-BP1 phosphorylation can recover during sustained rapamycin in a still-mTORC1/Raptor-dependent manner, defining the rapamycin-resistant component of 4E-BP1 regulation.

    Evidence Rapamycin time-course, Raptor/Rictor siRNA, kinase-dead mTOR in multiple cell types

    PMID:18955708

    Open questions at the time
    • Molecular basis for rapamycin resistance of specific sites not fully explained
  8. 2002 Medium

    Identified mTOR-independent inputs into 4E-BP1, showing UVB drives phosphorylation via p38/MSK1 and later that contraction drives phosphorylation insensitive to mTOR inhibition.

    Evidence Dominant-negative p38/MSK1 and inhibitors; Torin1-insensitive phosphorylation during electrical stimulation of rat muscle

    PMID:11777913 PMID:23707523

    Open questions at the time
    • Direct kinase identity for contraction-induced sites not pinned down
    • Physiological significance of non-canonical phosphorylation incompletely defined
  9. 2009 High

    Established transcriptional control of 4E-BP1 abundance as a regulatory layer: FOXO1, ATF4, and Smad4 induce it (driving translational repression, beta-cell ER-stress survival, and TGFbeta antiproliferation), while ERK/p38-Egr-1 and Snail repress it.

    Evidence Promoter/ChIP and reporter assays, inducible/transgenic and knockout models, siRNA, with functional proliferation, survival, and drug-resistance readouts

    PMID:12618431 PMID:17510058 PMID:18316032 PMID:19834456 PMID:29263324

    Open questions at the time
    • Combinatorial logic among these transcription factors in a single tissue not resolved
    • How transcriptional vs phospho-control are integrated in vivo unclear
  10. 2009 Medium

    Identified phosphorylation-independent regulators of 4E-BP1 activity (RhoE) and its protein stability via phosphorylation-coupled ubiquitination.

    Evidence RhoE overexpression with co-IP and cap-reporter assays; proteasome/phosphatase inhibitors and m7GTP affinity chromatography for ubiquitination

    PMID:17653084 PMID:19850923

    Open questions at the time
    • E3 ligase mediating phospho-coupled degradation not identified at this stage
    • RhoE mechanism of inhibiting phosphorylation undefined
  11. 2010 High

    Defined 4E-BP1 as the critical pathogenic effector of mTOR loss in the heart, since co-ablating 4E-BP1 rescues cardiomyopathy.

    Evidence Cardiac-specific mTOR conditional and mTOR/4E-BP1 double knockout mice with echocardiography, histology, and apoptosis assays

    PMID:20644257

    Open questions at the time
    • Specific mRNA targets responsible for cardiomyocyte death not identified
  12. 2010 Medium

    Connected 4E-BP1 to oncogenic signaling redundancy, showing it integrates AKT and ERK inputs on cap-dependent translation and governs tumor dependence on these pathways.

    Evidence siRNA, dominant-active 4E-BP1, AKT/MEK inhibitors, colony/proliferation assays in defined-mutation cancer lines

    PMID:20609351

    Open questions at the time
    • Direct kinase wiring of ERK input to 4E-BP1 not detailed
    • Single-lab cell-line study
  13. 2013 High

    Extended 4E-BP1's physiological reach to circadian entrainment, showing rhythmic mTOR/4E-BP1 control of VIP translation in the SCN sets clock amplitude and re-entrainment.

    Evidence 4E-BP1 knockout and Mtor heterozygous mice; VIP mRNA/protein, polysome fractionation, behavioral circadian assays

    PMID:23972597

    Open questions at the time
    • Whether VIP is the sole relevant translational target unclear
  14. 2012 Medium

    Uncovered a non-canonical mitotic role: 4E-BP1 localizes to centrosomes/spindles, interacts with PLK1, and its depletion causes mitotic defects, with CDK1 (Ser-83) generating a mitosis-specific isoform.

    Evidence Co-IP and in vitro PLK1/CDK1 kinase assays, phospho-specific antibodies and imaging, siRNA, flow cytometry, transformation assays; meiotic spindle localization in oocytes

    PMID:22918237 PMID:23852387 PMID:27402756 PMID:28272965

    Open questions at the time
    • Whether the mitotic role is translation-dependent or structural is unresolved
    • Functional significance of Ser-83 phosphorylation beyond transformation assays unclear
  15. 2016 Medium

    Defined translation-independent partners and outputs of 4E-BP1: unphosphorylated 4E-BP1 binds and destabilizes p21, coupling mTORC1 to cell-cycle control.

    Evidence Co-IP, p21 levels under mTORC1 inhibition, cell line and patient tissue correlation

    PMID:26832959

    Open questions at the time
    • Mechanism by which 4E-BP1 promotes p21 degradation not defined
    • Single Co-IP-based interaction study
  16. 2019 High

    Resolved the late C-terminal kinase as CDK12 and connected 4E-BP1 to selective translation of specific mRNA networks (CHK1, mitotic genes; DNA replication/repair factors when 4E-BP1 is lost).

    Evidence In vitro CDK12 kinase assay, RIP-seq and Ribo-seq, knockdown/knockout; genome-wide polysome profiling with 4E-BP1 depletion and eIF4A inhibitor rescue

    PMID:30819820 PMID:31201269 PMID:31672935

    Open questions at the time
    • Full mRNA selectivity rules of 4E-BP1 not defined
    • Coordination of CDK12 with mTORC1 priming in vivo incompletely mapped
  17. 2019 High

    Defined 4E-BP1 protein stability control by O-GlcNAcylation, which suppresses CUL3-mediated ubiquitination via a PEST motif, identifying the relevant E3 ligase machinery.

    Evidence Ribosome profiling, O-GlcNAcase inhibitor, knockout mice, cycloheximide chase, CUL3 co-IP

    PMID:30733333

    Open questions at the time
    • Substrate adaptor linking CUL3 to 4E-BP1 not identified
    • Interplay between O-GlcNAcylation and phospho-coupled degradation unresolved
  18. 2021 High

    Provided the structural-mechanistic basis at atomic resolution: bivalent RAIP/TOS binding to two Raptor sites creates avidity tethering that orients disordered 4E-BP1 to the mTOR site and drives phosphorylation hierarchy and differential rapamycin sensitivity.

    Evidence NMR spectroscopy of 4E-BP1/Raptor interaction with in vitro phosphorylation validation

    PMID:33852892

    Open questions at the time
    • Structure of the full mTORC1–4E-BP1 complex not solved
    • Conformational coupling to eIF4E release not directly visualized
  19. 2023 Medium

    Extended 4E-BP1 function to mitochondrial homeostasis and aging, showing it supports respiratory complex III stability and PGC-1alpha translation to control senescence and metabolism.

    Evidence CRISPR knockout and rescue in hMSCs with respiration/ROS/senescence assays; muscle-specific 4E-BP1 transgenic mice with polysome fractionation and metabolic phenotyping

    PMID:26121750 PMID:36929036

    Open questions at the time
    • Direct mechanism linking 4E-BP1 to complex III subunit translation unresolved
    • Whether effects are cap-translation-dependent not fully established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the canonical translational-repressor function is mechanistically integrated with the non-canonical centrosome/spindle, p21, and mitochondrial roles — and whether these share or bypass the eIF4E-binding mechanism — remains unresolved.
  • No unified model reconciling translation-dependent and translation-independent functions
  • Substrate adaptor for CUL3-mediated turnover unidentified
  • Tissue-specific mRNA target sets only partially mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0045182 translation regulator activity 3 GO:0098772 molecular function regulator activity 2 GO:0140110 transcription regulator activity 2 GO:0140313 molecular sequestering activity 2
Localization
GO:0005815 microtubule organizing center 2 GO:0005856 cytoskeleton 2 GO:0005829 cytosol 1
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3
Partners
CDK1CDK12CDKN1ACUL3EIF4EMTORPLK1RPTOR
Complex memberships
mTORC1 (transient substrate via Raptor tethering)

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 PHAS-I (4E-BP1) binds to eIF4E and inhibits protein synthesis when unphosphorylated; MAP kinase phosphorylates Ser-64, which prevents PHAS-I from binding eIF4E, linking MAP kinase signaling to translational control. In vitro binding assay with immobilized PHAS-I, mRNA cap affinity resin, and kinase assays in adipocyte extracts Science High 7939721
1994 PHAS-I (4E-BP1) is a 117-amino-acid heat-stable protein that is phosphorylated in response to insulin and growth factors; it is expressed at highest levels in fat and skeletal muscle. cDNA cloning, in vitro translation, SDS-PAGE, Western blot, Northern blot Proceedings of the National Academy of Sciences of the United States of America Medium 8170978
1995 Phosphorylation of PHAS-I by growth factors (PDGF, IGF-I) promotes dissociation of the PHAS-I·eIF-4E complex; both effects are abolished by rapamycin, placing PHAS-I downstream of the rapamycin-sensitive (mTOR/p70S6K) pathway in smooth muscle cells. Co-immunoprecipitation, phosphorylation assay, rapamycin treatment, p70S6K activity assay in rat aortic smooth muscle cells Proceedings of the National Academy of Sciences of the United States of America Medium 7638171
1996 Rapamycin blocks 4E-BP1 phosphorylation and specifically inhibits cap-dependent (but not cap-independent) translation; dephosphorylation/activation of 4E-BP1 is the mechanistic basis for rapamycin's suppression of cap-dependent translation. In vitro translation assays comparing cap-dependent vs. IRES-driven reporters; Western blot of 4E-BP1 phosphorylation in rapamycin-treated NIH 3T3 cells; FK506 competition The EMBO journal High 8599949
1996 4E-BP1 phosphorylation is mediated by the FRAP/mTOR–p70S6K pathway and is independent of MAP kinase (ERK/p42mapk), established by insulin stimulation studies in cells lacking MAP kinase activation and use of MEK inhibitors. Pharmacological inhibitors (rapamycin, wortmannin, SQ20006), receptor point mutants (PDGFR 740F/751F), kinase activity assays in multiple cell types Proceedings of the National Academy of Sciences of the United States of America High 8633019
1996 Both insulin and diabetes regulate PHAS-I·eIF-4E complex formation in rat skeletal muscle through changes in PHAS-I phosphorylation (not eIF-4E phosphorylation), directly demonstrating this axis controls muscle protein synthesis in vivo. Western blot and co-immunoprecipitation of eIF-4E/PHAS-I complexes in rat skeletal muscle; insulin and alloxan-diabetes models The American journal of physiology Medium 8779938
1997 mTOR (FRAP) directly phosphorylates PHAS-I (4E-BP1) on serine and threonine residues in vitro; this phosphorylation inhibits 4E-BP1 binding to eIF-4E and the rapamycin-sensitive kinase activity of mTOR is required for PHAS-I phosphorylation in cells. In vitro kinase assay with mTOR immunoprecipitate; phospho-amino acid analysis; in vivo rapamycin treatment of insulin-stimulated HEK293 cells Science High 9204908
1997 mTOR mutants resistant to rapamycin·FKBP12 protect eIF4E-BP1 from rapamycin-induced dephosphorylation, and this protection requires an active mTOR catalytic domain, demonstrating that mTOR directly regulates 4E-BP1 phosphorylation (parallel to, not downstream of, S6K1). Transient transfection of rapamycin-resistant mTOR and kinase-dead mTOR mutants; Western blot of 4E-BP1 phosphorylation The Journal of biological chemistry High 9334222
1998 RAFT1/mTOR directly phosphorylates 4E-BP1 on Thr-36 and Thr-45 in vitro; serum stimulates RAFT1 kinase activity with kinetics parallel to 4E-BP1 phosphorylation; phosphorylation of Thr-45 is identified as the major regulator of the 4E-BP1–eIF-4E interaction in vivo. In vitro kinase assay with immunoprecipitated RAFT1; phosphopeptide mapping; in vivo phosphorylation analysis Proceedings of the National Academy of Sciences of the United States of America High 9465032
1998 The PI3K/Akt pathway is required for 4E-BP1 phosphorylation: a dominant-negative Akt blocks insulin-induced 4E-BP1 phosphorylation; activated Akt induces 4E-BP1 phosphorylation on the same sites as serum, but this requires FRAP/mTOR activity downstream. Dominant-negative and constitutively-active Akt mutant expression; wortmannin/rapamycin inhibitors; phosphorylation-site analysis by Western blot and co-IP with eIF4E Genes & development High 9472019
1999 4E-BP1 phosphorylation by FRAP/mTOR follows a hierarchical two-step mechanism: mTOR first phosphorylates Thr-37 and Thr-46 (priming events) even when 4E-BP1 is bound to eIF4E, and these are required for subsequent phosphorylation of carboxy-terminal serum-sensitive sites (Ser-65, Thr-70) that cause eIF4E release. In vitro FRAP/mTOR kinase assays; phosphopeptide mapping; mass spectrometry identification of phosphorylation sites; mutational analysis of Thr-37/Thr-46 Genes & development High 10364159
1999 An mTOR-associated kinase (distinct from mTOR itself) phosphorylates 4E-BP1 within a peptide containing Ser-64 and Thr-69, and this phosphorylation (predominantly at Ser-64) is sufficient to dissociate 4E-BP1 from eIF-4E. mTOR immunoprecipitate fractionation; in vitro kinase assay; co-immunoprecipitation with eIF4E FEBS letters Medium 10471835
1999 Akt (PKB), but not atypical PKCλ, is required for insulin-induced 4E-BP1 phosphorylation, demonstrated using an Akt mutant (Akt-AA) that blocks insulin activation. Dominant-negative Akt and kinase-defective PKCλ expression in L6 myotubes and CHO cells; Western blot for 4E-BP1 phosphorylation The Journal of biological chemistry Medium 10400692
2002 UVB irradiation induces 4E-BP1 phosphorylation at Thr-36, Thr-45, Ser-64, and Thr-69 through the p38/MSK1 pathway (not PI3K/Akt), causing dissociation of 4E-BP1 from eIF-4E; dominant-negative p38 or MSK1 block this phosphorylation. p38 and MSK1 inhibitors; dominant-negative kinase mutant expression; in vivo phosphorylation analysis; co-immunoprecipitation with eIF4E The Journal of biological chemistry Medium 11777913
2003 Both the N-terminal RAIP motif and the C-terminal TOS motif of PHAS-I/4E-BP1 are required for efficient phosphorylation by mTOR in vitro and in vivo; wild-type but not RAIP- or TOS-mutant PHAS-I co-immunoprecipitates with raptor, and raptor overexpression enhances mTOR phosphorylation of wild-type but not mutant PHAS-I. In vitro mTOR kinase assay with RAIP/TOS mutant recombinant proteins; co-immunoprecipitation with HA-tagged raptor; in vivo phosphorylation assay The Journal of biological chemistry High 12665511
2003 A functional TOS motif in 4E-BP1 is required for binding to raptor (mTOR-associated protein), for efficient in vitro phosphorylation by the mTOR/raptor complex, for multisite in vivo phosphorylation, and for eIF4E release; a TOS-motif mutation (F114A) reduces cell size. In vitro mTOR/raptor complex kinase assay; co-immunoprecipitation of raptor and 4E-BP1; in vivo phosphorylation; cell size measurement Current biology High 12747827
2003 Ser-64 and Ser-111 phosphorylation of PHAS-I are dispensable for insulin-stimulated dissociation from eIF4E; phosphorylation of the Thr sites (Thr-36/45, Thr-69) is the primary determinant of eIF4E release. Alanine substitution mutants (A64, A111) of PHAS-I; in vivo phosphorylation analysis; eIF4E binding assay The Journal of biological chemistry Medium 14507920
2007 FOXO1 transcription factor binds the 4E-BP1 gene promoter and induces its expression in skeletal muscle; increased 4E-BP1 abundance reduces Raptor–mTOR association, decreases p70S6K phosphorylation, and attenuates protein synthesis, linking FOXO1 to translational repression via 4E-BP1 upregulation. Inducible FOXO1-ER fusion protein system; promoter-binding assay (ChIP); Western blot for 4E-BP1, Raptor, mTOR; [14C]phenylalanine incorporation; transgenic mouse model The Journal of biological chemistry Medium 17510058
2007 4E-BP1 is a substrate for polyubiquitination; hyperphosphorylated forms of 4E-BP1 are simultaneously polyubiquitinated, bind eIF4E poorly, and are subject to proteasomal degradation. Phosphatase inhibition (calyculin A) reduces 4E-BP1 half-life by promoting ubiquitination of phosphorylated forms. Proteasome inhibitor (MG132), phosphatase inhibitor (calyculin A), m7GTP-Sepharose affinity chromatography, cycloheximide chase Oncogene Medium 17653084
2008 4E-BP1 gene is a direct transcriptional target of ATF4; ATF4-mediated induction of 4E-BP1 is required for beta cell survival under ER stress, as 4E-BP1 deletion increases susceptibility to ER stress-mediated apoptosis and exacerbates hyperglycemia in diabetic mouse models. Reporter gene assay for Eif4ebp1 promoter; Eif4ebp1 knockout mice; siRNA knockdown in MIN6 cells; ER stress induction with tunicamycin/thapsigargin Cell metabolism High 18316032
2008 Rapamycin differentially inhibits S6K versus 4E-BP1: S6K activity is inhibited throughout rapamycin treatment, but 4E-BP1 phosphorylation recovers within 6 h despite continued rapamycin exposure; this recovered phosphorylation is rapamycin-resistant but still requires mTOR and Raptor (mTORC1 activity). Rapamycin time-course experiments; siRNA knockdown of Raptor and Rictor; mTOR kinase-dead mutants; phospho-Western blot in multiple cell types Proceedings of the National Academy of Sciences of the United States of America High 18955708
2009 Smad4 directly binds a conserved element in the 4E-BP1 gene promoter and enhances its transcription; TGFβ-mediated antiproliferative signaling requires 4E-BP1, as knockdown or knockout of 4E-BP1 abolishes TGFβ growth inhibition. Promoter-binding/reporter assays; co-Smad manipulation; 4E-BP1 siRNA/shRNA knockdown in human cancer cells; 4E-BP1-/- mouse embryonic fibroblasts The EMBO journal High 19834456
2009 RhoE inhibits 4E-BP1 phosphorylation in response to extracellular stimuli without affecting mTOR activity (as evidenced by normal S6K phosphorylation and mTOR/Raptor dynamics), prevents eIF4E release from 4E-BP1, and thereby inhibits cap-dependent translation including cyclin D1 and c-Myc expression. RhoE overexpression; co-immunoprecipitation of 4E-BP1/eIF4E; phospho-Western blot for mTOR substrates; cap-dependent translation reporter assays The Journal of biological chemistry Medium 19850923
2010 4E-BP1 and ERK signaling pathways converge on cap-dependent translation; AKT independence in tumors with comutated PIK3CA/PTEN and ERK pathways is mediated by redundant 4E-BP1 regulation; 4E-BP1 knockdown reduces tumor dependence on AKT/ERK signaling, while dominant-active 4E-BP1 restores sensitivity. siRNA knockdown of 4E-BP1; dominant-active 4E-BP1 mutant expression; AKT and MEK inhibitor treatment; colony formation and proliferation assays in cancer cell lines with defined mutations Cancer cell Medium 20609351
2010 In mouse cardiomyocytes, ablation of mTOR leads to accumulation of unphosphorylated (active) 4E-BP1, resulting in dilated cardiomyopathy; genetic co-ablation of 4E-BP1 together with mTOR markedly rescues apoptosis, cardiac function, and survival, demonstrating that excessive 4E-BP1 activity mediates the cardiac phenotype of mTOR loss. Cardiac-specific mTOR conditional knockout mice; double mTOR/4E-BP1 knockout mice; echocardiography; histology; apoptosis assays The Journal of clinical investigation High 20644257
2012 Phosphorylated 4E-BP1 (Thr37/46) co-localizes with PLK1 at centrosomes during mitosis; 4E-BP1 directly interacts with PLK1 in vitro and in vivo via its C-terminal aa 77-118; PLK1 phosphorylates 4E-BP1 in vitro; 4E-BP1 depletion causes polyploidy, chromosomal misalignment, and multipolar spindles. Co-immunoprecipitation; in vitro kinase assay with PLK1; siRNA knockdown; immunofluorescence co-localization; flow cytometry Cell cycle Medium 22918237
2013 mTOR/4E-BP1 signaling rhythmically controls VIP mRNA translation in the suprachiasmatic nucleus (SCN); 4E-BP1 KO increases VIP expression and amplitude of molecular rhythms, accelerates re-entrainment to shifted light/dark cycles, and increases resistance to constant-light disruption, while Mtor+/- mice show opposite effects. 4E-BP1 knockout mice; Mtor heterozygous mice; VIP protein and mRNA measurement; behavioral circadian assays; polysome fractionation Neuron High 23972597
2013 Phosphorylated EIF4EBP1 (4E-BP1) localizes to the meiotic spindle in mouse oocytes; different phosphorylation-site variants (pThr37/46, pSer65, pThr70) appear at distinct spindle positions at different meiotic stages, suggesting spatially regulated translational control. 4E-BP1 is the only 4E-BP isoform present as protein in oocytes. cDNA microarray enrichment assay on isolated MII spindles; immunofluorescence with phospho-site-specific antibodies; Western blot Genetics Medium 23852387
2016 CDK1 phosphorylates 4E-BP1 at Ser-83 during mitosis, generating a mitosis-specific hyperphosphorylated δ-isoform; pSer83 accumulates at centrosomes during prophase/metaphase; Ser83 phosphorylation does not affect general cap-dependent translation but the S83A mutant partially reverses Merkel cell polyomavirus small T antigen-induced cell transformation. Mass spectrometry identification of CDK1 phosphorylation sites; phospho-Ser83-specific antibody; co-localization imaging; S83A mutant expression; transformation assay Proceedings of the National Academy of Sciences of the United States of America Medium 27402756
2016 Non-phosphorylated 4E-BP1 interacts with p21 (CDKN1A) and promotes its degradation; mTORC1-mediated phosphorylation of 4E-BP1 prevents this interaction, stabilizing p21 protein levels, thereby linking mTORC1 activity to p21-dependent cell cycle control. Co-immunoprecipitation; Western blot for p21 levels under mTORC1 inhibition; cell line and patient tissue correlation analysis Nature communications Medium 26832959
2017 Snail transcription factor directly binds three E-boxes in the human 4E-BP1 promoter and represses 4E-BP1 transcription; Snail overexpression reduces 4E-BP1 expression, promotes cap-dependent translation, and confers resistance to mTOR kinase inhibitors; genetic or pharmacological Snail inhibition restores 4E-BP1 and resensitizes cancer cells. ChIP assay; promoter reporter assay; ectopic Snail expression and knockdown; Western blot; polysome profiling; tumor xenograft models Nature communications High 29263324
2019 CDK12 phosphorylates 4E-BP1 at Ser-65 and Thr-70 (Ser-Pro sites) subsequent to mTORC1 priming phosphorylations at T37/T46, controlling 4E-BP1 exchange with eIF4G at 5'-caps of CHK1 and other mTORC1-target mRNAs; RIP-seq and Ribo-seq demonstrate CDK12 regulates a specific translation network including mitotic/centromere genes. In vitro CDK12 kinase assay; RIP-seq; ribosome profiling (Ribo-seq); CDK12 knockdown/knockout; confocal imaging of mitotic defects Genes & development High 30819820
2019 4E-BP1 loss in pancreatic cancer cells results in selective upregulation of translational efficiency of mRNAs encoding DNA replication/repair proteins (RRM2, CDC6), rendering DNA replication insensitive to mTOR inhibitors; this is rescued by eIF4A inhibitors (silvestrol derivatives). Genome-wide polysome profiling; 4E-BP1 depletion; Western blot for CDC6/RRM2; patient sample correlation; 4E-BP1/2 DKO mouse pancreatitis model JCI insight Medium 31672935
2019 The mitotic δ-isoform of 4E-BP1 (hyperphosphorylated at Thr-70, Ser-83, Ser-101) does not interact with eIF4E; a distinct EB-γ isoform phosphorylated at Thr-70/Ser-83/Ser-101 retains eIF4E binding during mitosis; eIF4E:eIF4G interaction is maintained or increased in mitosis, indicating active translation initiation during mitosis. 2D gel electrophoresis; proximity ligation assays; phospho-site-specific analysis; single-cell nascent protein synthesis assay; eIF4G RIP-seq The Journal of biological chemistry Medium 31201269
2019 O-GlcNAcylation of 4E-BP1 (within a PEST motif) stabilizes 4E-BP1 protein by reducing its ubiquitination and proteasomal degradation; elevated 4E-BP1 in diabetic retina sequesters eIF4E and alters mRNA translation selection; a CUL3-containing E3 ubiquitin ligase complex regulates 4E-BP1 polyubiquitination via the PEST motif. Ribosome profiling (retina); O-GlcNAcase inhibitor (Thiamet G); 4E-BP1/2 knockout mice; cycloheximide chase; CUL3 co-immunoprecipitation The Journal of biological chemistry High 30733333
2021 4E-BP1 is tethered to mTORC1 via dual binding: its N-terminal RAIP motif and C-terminal TOS motif bind to two separate sites on Raptor, creating avidity-based tethering that orients the central region of intrinsically disordered 4E-BP1 toward the mTOR kinase site. Phosphorylation-induced conformational switching of 4E-BP1 explains the hierarchy of site phosphorylation and the differential rapamycin sensitivity of individual sites; mTORC1 recognizes both free and eIF4E-bound 4E-BP1. NMR spectroscopy monitoring of 4E-BP1/Raptor interaction; in vitro phosphorylation assays; structural analysis of intrinsically disordered 4E-BP1 Molecular cell High 33852892
2019 4E-BP1 in mTOR-ablated cardiomyocytes inhibits translation initiation; genetic co-ablation of 4E-BP1 with mTOR rescues cardiac apoptosis, heart function, and survival, establishing 4E-BP1 as the key downstream effector of mTOR-dependent cardiomyocyte viability. Cardiac-specific double KO (mTOR + 4E-BP1) mice; echocardiography; apoptosis and autophagy assays; pressure overload model The Journal of clinical investigation High 20644257
2013 mTOR-independent phosphorylation of 4E-BP1 occurs during muscle contraction (high-frequency electrical stimulation), is associated with release of 4E-BP1 from eIF4E, and is not blocked by the mTOR inhibitor Torin1; MEK/ERK/RSK1 pathway mediates mTOR-independent phosphorylation of eIF4B during contraction. In situ electrical stimulation of rat skeletal muscle; Torin1 (mTOR inhibitor) treatment; MEK/ERK/RSK1 inhibitors; Western blot; co-immunoprecipitation Cellular signalling Medium 23707523
2016 ERK and p38 MAP kinases decrease 4E-BP1 protein and mRNA expression through induction of the transcription factor Egr-1, which represses the 4e-bp1 promoter; this identifies a new pathway whereby ERK/p38 regulate translational capacity through transcriptional control of 4E-BP1 levels. PMA/GM-CSF stimulation; ERK/p38 inhibitors; dominant-negative Egr (ZnEgr) expression; 4e-bp1 promoter reporter assay; Northern and Western blot The Journal of biological chemistry Medium 12618431
2017 During mouse oocyte meiotic resumption, CDK1 and mTOR both phosphorylate 4E-BP1 at the spindle; CDK1 acts via phosphorylation and activation of mTOR; pThr70 of 4E-BP1 co-localizes with CDK1 and phospho-mTOR on the spindle; dominant-negative 4E-BP1 impairs translation and causes spindle abnormalities; PLK1 does not phosphorylate 4E-BP1 in this context. Immunofluorescence with phospho-site-specific antibodies; dominant-negative 4E-BP1 expression; CDK1/mTOR/PLK1 inhibitors; in vitro translation assay Cell cycle Medium 28272965
2023 4E-BP1 expression decreases during human mesenchymal stem cell (hMSC) senescence; 4E-BP1 knockout destabilizes mitochondrial respiration complex III subunits (including UQCRC2), increases mitochondrial ROS, and accelerates senescence; ectopic 4E-BP1 expression rescues these defects in both 4E-BP1-deficient and physiologically aged hMSCs. CRISPR-Cas9 4E-BP1 knockout in hMSCs; ectopic overexpression; mitochondrial respiration assay; Western blot for complex III subunits; ROS measurement; senescence assays Protein & cell Medium 36929036
2015 Muscle-specific 4E-BP1 transgenic expression directly increases PGC-1α translation and enhances mitochondrial respiratory function; it also promotes FGF21 secretion, preserving brown adipose tissue metabolism and protecting against age- and diet-induced insulin resistance and metabolic decline. Transgenic mice with skeletal muscle-specific 4E-BP1 expression; polysome fractionation for PGC-1α translation; metabolic phenotyping; FGF21 ELISA; adipose tissue analysis The Journal of clinical investigation High 26121750

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism. Genes & development 1103 10364159
1998 RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1. Proceedings of the National Academy of Sciences of the United States of America 952 9465032
1997 Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin. Science (New York, N.Y.) 815 9204908
1998 4E-BP1, a repressor of mRNA translation, is phosphorylated and inactivated by the Akt(PKB) signaling pathway. Genes & development 734 9472019
2008 Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation. Proceedings of the National Academy of Sciences of the United States of America 700 18955708
1994 PHAS-I as a link between mitogen-activated protein kinase and translation initiation. Science (New York, N.Y.) 617 7939721
1996 Rapamycin blocks the phosphorylation of 4E-BP1 and inhibits cap-dependent initiation of translation. The EMBO journal 576 8599949
1997 Regulation of eIF-4E BP1 phosphorylation by mTOR. The Journal of biological chemistry 414 9334222
2003 TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function. Current biology : CB 401 12747827
2010 4E-BP1 is a key effector of the oncogenic activation of the AKT and ERK signaling pathways that integrates their function in tumors. Cancer cell 348 20609351
2014 mTORC1 drives HIF-1α and VEGF-A signalling via multiple mechanisms involving 4E-BP1, S6K1 and STAT3. Oncogene 326 24931163
2010 MTORC1 regulates cardiac function and myocyte survival through 4E-BP1 inhibition in mice. The Journal of clinical investigation 293 20644257
2016 4E-BP1, a multifactor regulated multifunctional protein. Cell cycle (Georgetown, Tex.) 262 26901143
2000 4E-BP1 and S6K1: translational integration sites for nutritional and hormonal information in muscle. American journal of physiology. Endocrinology and metabolism 234 11001751
1996 4E-BP1 phosphorylation is mediated by the FRAP-p70s6k pathway and is independent of mitogen-activated protein kinase. Proceedings of the National Academy of Sciences of the United States of America 226 8633019
1995 cAMP- and rapamycin-sensitive regulation of the association of eukaryotic initiation factor 4E and the translational regulator PHAS-I in aortic smooth muscle cells. Proceedings of the National Academy of Sciences of the United States of America 208 7638171
1996 Stimulation of protein synthesis, eukaryotic translation initiation factor 4E phosphorylation, and PHAS-I phosphorylation by insulin requires insulin receptor substrate 1 and phosphatidylinositol 3-kinase. Molecular and cellular biology 205 8649395
1996 Activation of the translational suppressor 4E-BP1 following infection with encephalomyocarditis virus and poliovirus. Proceedings of the National Academy of Sciences of the United States of America 200 8643618
2015 Pharmacological targeting of the protein synthesis mTOR/4E-BP1 pathway in cancer-associated fibroblasts abrogates pancreatic tumour chemoresistance. EMBO molecular medicine 178 25834145
2019 The mTORC1/4E-BP1 axis represents a critical signaling node during fibrogenesis. Nature communications 169 30602778
2006 Rapamycin inhibits cell motility by suppression of mTOR-mediated S6K1 and 4E-BP1 pathways. Oncogene 165 16715128
2008 ATF4-mediated induction of 4E-BP1 contributes to pancreatic beta cell survival under endoplasmic reticulum stress. Cell metabolism 162 18316032
2016 Eukaryotic initiation factor 4E-binding protein 1 (4E-BP1): a master regulator of mRNA translation involved in tumorigenesis. Oncogene 146 26829052
1996 Regulation of both glycogen synthase and PHAS-I by insulin in rat skeletal muscle involves mitogen-activated protein kinase-independent and rapamycin-sensitive pathways. The Journal of biological chemistry 144 8617780
1994 Molecular cloning and tissue distribution of PHAS-I, an intracellular target for insulin and growth factors. Proceedings of the National Academy of Sciences of the United States of America 126 8170978
2013 Translational control of entrainment and synchrony of the suprachiasmatic circadian clock by mTOR/4E-BP1 signaling. Neuron 122 23972597
2004 Arginine and Leucine regulate p70 S6 kinase and 4E-BP1 in intestinal epithelial cells. International journal of molecular medicine 118 15010853
1996 Insulin and diabetes cause reciprocal changes in the association of eIF-4E and PHAS-I in rat skeletal muscle. The American journal of physiology 115 8779938
2000 Regulation of protein kinase B and 4E-BP1 by oxidative stress in cardiac myocytes. Circulation research 114 10864916
2008 AMPK activation attenuates S6K1, 4E-BP1, and eEF2 signaling responses to high-frequency electrically stimulated skeletal muscle contractions. Journal of applied physiology (Bethesda, Md. : 1985) 111 18187610
2018 Inhibition of mTORC1 by lncRNA H19 via disrupting 4E-BP1/Raptor interaction in pituitary tumours. Nature communications 106 30397197
2015 Muscle-specific 4E-BP1 signaling activation improves metabolic parameters during aging and obesity. The Journal of clinical investigation 106 26121750
2003 Two motifs in the translational repressor PHAS-I required for efficient phosphorylation by mammalian target of rapamycin and for recognition by raptor. The Journal of biological chemistry 94 12665511
2013 Arginine, leucine, and glutamine stimulate proliferation of porcine trophectoderm cells through the MTOR-RPS6K-RPS6-EIF4EBP1 signal transduction pathway. Biology of reproduction 89 23486913
1996 Control of the translational regulators PHAS-I and PHAS-II by insulin and cAMP in 3T3-L1 adipocytes. The Journal of biological chemistry 89 8939971
2015 Tanshinone IIA inhibits HIF-1α and VEGF expression in breast cancer cells via mTOR/p70S6K/RPS6/4E-BP1 signaling pathway. PloS one 85 25659153
2007 FOXO1 regulates the expression of 4E-BP1 and inhibits mTOR signaling in mammalian skeletal muscle. The Journal of biological chemistry 84 17510058
1999 Requirement for Akt (protein kinase B) in insulin-induced activation of glycogen synthase and phosphorylation of 4E-BP1 (PHAS-1). The Journal of biological chemistry 83 10400692
1999 Dissociation of the eukaryotic initiation factor-4E/4E-BP1 complex involves phosphorylation of 4E-BP1 by an mTOR-associated kinase. FEBS letters 82 10471835
2014 Rotenone induction of hydrogen peroxide inhibits mTOR-mediated S6K1 and 4E-BP1/eIF4E pathways, leading to neuronal apoptosis. Toxicological sciences : an official journal of the Society of Toxicology 80 25304210
2011 S6K1 and 4E-BP1 are independent regulated and control cellular growth in bladder cancer. PloS one 80 22110663
2021 The dynamic mechanism of 4E-BP1 recognition and phosphorylation by mTORC1. Molecular cell 74 33852892
2010 Expression and distribution of mTOR, p70S6K, 4E-BP1, and their phosphorylated counterparts in rat dorsal root ganglion and spinal cord dorsal horn. Brain research 72 20399760
2012 mTOR-independent 4E-BP1 phosphorylation is associated with cancer resistance to mTOR kinase inhibitors. Cell cycle (Georgetown, Tex.) 70 22262166
2019 CDK12 phosphorylates 4E-BP1 to enable mTORC1-dependent translation and mitotic genome stability. Genes & development 69 30819820
2019 4E-BP1 Is a Tumor Suppressor Protein Reactivated by mTOR Inhibition in Head and Neck Cancer. Cancer research 66 30894372
2002 Phosphorylation of 4E-BP1 is mediated by the p38/MSK1 pathway in response to UVB irradiation. The Journal of biological chemistry 64 11777913
2013 Pancreatic tumours escape from translational control through 4E-BP1 loss. Oncogene 57 23563181
2007 Effects of protein phosphorylation on ubiquitination and stability of the translational inhibitor protein 4E-BP1. Oncogene 57 17653084
2016 Increased 4E-BP1 Expression Protects against Diet-Induced Obesity and Insulin Resistance in Male Mice. Cell reports 54 27498874
2003 ERK and p38 inhibit the expression of 4E-BP1 repressor of translation through induction of Egr-1. The Journal of biological chemistry 54 12618431
2016 MicroRNAs 125a and 125b inhibit ovarian cancer cells through post-transcriptional inactivation of EIF4EBP1. Oncotarget 53 26646586
2005 PPAR-gamma inhibits ANG II-induced cell growth via SHIP2 and 4E-BP1. American journal of physiology. Heart and circulatory physiology 52 16155101
2002 Alcohol impairs insulin and IGF-I stimulation of S6K1 but not 4E-BP1 in skeletal muscle. American journal of physiology. Endocrinology and metabolism 52 12376318
2007 The endoplasmic reticulum stress-inducible protein Niban regulates eIF2alpha and S6K1/4E-BP1 phosphorylation. Biochemical and biophysical research communications 51 17588536
2009 4E-BP1 is a target of Smad4 essential for TGFbeta-mediated inhibition of cell proliferation. The EMBO journal 49 19834456
2021 PP2A-mTOR-p70S6K/4E-BP1 axis regulates M1 polarization of pulmonary macrophages and promotes ambient particulate matter induced mouse lung injury. Journal of hazardous materials 48 34740159
1997 Inactivation of eIF2B and phosphorylation of PHAS-I in heat-shocked rat hepatoma cells. The Journal of biological chemistry 48 9341116
2012 Constitutive phosphorylation of the mTORC2/Akt/4E-BP1 pathway in newly derived canine hemangiosarcoma cell lines. BMC veterinary research 46 22839755
2005 Expression of the eukaryotic translation initiation factor 4E (eIF4E) and 4E-BP1 in esophageal cancer. Clinical biochemistry 46 16375881
2016 mTORC1 signalling and eIF4E/4E-BP1 translation initiation factor stoichiometry influence recombinant protein productivity from GS-CHOK1 cells. The Biochemical journal 45 27760840
2013 Mammalian target of rapamycin-independent S6K1 and 4E-BP1 phosphorylation during contraction in rat skeletal muscle. Cellular signalling 45 23707523
2013 Phosphorylation of eIF4GII and 4E-BP1 in response to nocodazole treatment: a reappraisal of translation initiation during mitosis. Cell cycle (Georgetown, Tex.) 45 24091728
1997 Adenovirus infection inactivates the translational inhibitors 4E-BP1 and 4E-BP2. Virology 45 9344920
2016 Mitotic protein kinase CDK1 phosphorylation of mRNA translation regulator 4E-BP1 Ser83 may contribute to cell transformation. Proceedings of the National Academy of Sciences of the United States of America 44 27402756
2016 Stabilization of p21 by mTORC1/4E-BP1 predicts clinical outcome of head and neck cancers. Nature communications 43 26832959
2000 Amino acids regulate skeletal muscle PHAS-I and p70 S6-kinase phosphorylation independently of insulin. American journal of physiology. Endocrinology and metabolism 42 10913029
2019 Frenolicin B Targets Peroxiredoxin 1 and Glutaredoxin 3 to Trigger ROS/4E-BP1-Mediated Antitumor Effects. Cell chemical biology 39 30661989
2013 Association of maternal mRNA and phosphorylated EIF4EBP1 variants with the spindle in mouse oocytes: localized translational control supporting female meiosis in mammals. Genetics 39 23852387
2017 Regulation of 4E-BP1 activity in the mammalian oocyte. Cell cycle (Georgetown, Tex.) 37 28272965
2004 Strain-induced vascular endothelial cell proliferation requires PI3K-dependent mTOR-4E-BP1 signal pathway. American journal of physiology. Heart and circulatory physiology 36 15591103
2022 The mTOR/4E-BP1/eIF4E Signalling Pathway as a Source of Cancer Drug Targets. Current medicinal chemistry 34 35209811
2017 Snail determines the therapeutic response to mTOR kinase inhibitors by transcriptional repression of 4E-BP1. Nature communications 34 29263324
2012 Phosphorylation of 4E-BP1 in the mammalian brain is not altered by LRRK2 expression or pathogenic mutations. PloS one 34 23082216
2009 Inhibition of 4E-BP1 sensitizes U87 glioblastoma xenograft tumors to irradiation by decreasing hypoxia tolerance. International journal of radiation oncology, biology, physics 34 19251093
2008 Associations between multiple system atrophy and polymorphisms of SLC1A4, SQSTM1, and EIF4EBP1 genes. Movement disorders : official journal of the Movement Disorder Society 34 18442140
2017 Luteolin, a natural flavonoid, inhibits methylglyoxal induced apoptosis via the mTOR/4E-BP1 signaling pathway. Scientific reports 33 28801605
2019 eIF4A inhibition circumvents uncontrolled DNA replication mediated by 4E-BP1 loss in pancreatic cancer. JCI insight 31 31672935
2012 4E-BP1 participates in maintaining spindle integrity and genomic stability via interacting with PLK1. Cell cycle (Georgetown, Tex.) 31 22918237
2023 4E-BP1 counteracts human mesenchymal stem cell senescence via maintaining mitochondrial homeostasis. Protein & cell 30 36929036
2011 Insights into 4E-BP1 and p53 mediated regulation of accelerated cell senescence. Oncotarget 30 21399233
2011 The effect of p-4E-BP1 and p-eIF4E on cell proliferation in a breast cancer model. International journal of oncology 30 21750861
2015 Targeting mTOR/p70S6K/glycolysis signaling pathway restores glucocorticoid sensitivity to 4E-BP1 null Burkitt Lymphoma. BMC cancer 29 26189041
2009 RhoE inhibits 4E-BP1 phosphorylation and eIF4E function impairing cap-dependent translation. The Journal of biological chemistry 29 19850923
2016 The Translational Repressor 4E-BP1 Contributes to Diabetes-Induced Visual Dysfunction. Investigative ophthalmology & visual science 28 26998719
2018 The mTOR Targets 4E-BP1/2 Restrain Tumor Growth and Promote Hypoxia Tolerance in PTEN-driven Prostate Cancer. Molecular cancer research : MCR 27 29453322
2022 Expression of 4E-BP1 in juvenile mice alleviates mTOR-induced neuronal dysfunction and epilepsy. Brain : a journal of neurology 26 34849602
2019 Metastasis-associated protein 1, modulated by miR-30c, promotes endometrial cancer progression through AKT/mTOR/4E-BP1 pathway. Gynecologic oncology 26 30979588
2019 O-GlcNAcylation alters the selection of mRNAs for translation and promotes 4E-BP1-dependent mitochondrial dysfunction in the retina. The Journal of biological chemistry 25 30733333
2020 4E-BP1 Protects Neurons from Misfolded Protein Stress and Parkinson's Disease Toxicity by Inducing the Mitochondrial Unfolded Protein Response. The Journal of neuroscience : the official journal of the Society for Neuroscience 24 33046555
2019 4E-BP1 and 4E-BP2 double knockout mice are protected from aging-associated sarcopenia. Journal of cachexia, sarcopenia and muscle 24 30927336
2006 Regulation of translation factors eIF4GI and 4E-BP1 during recovery of protein synthesis from inhibition by p53. Cell death and differentiation 24 16990847
1997 Insulin activates a PD 098059-sensitive kinase that is involved in the regulation of p70S6K and PHAS-I. FEBS letters 24 9202140
2019 Mitosis-related phosphorylation of the eukaryotic translation suppressor 4E-BP1 and its interaction with eukaryotic translation initiation factor 4E (eIF4E). The Journal of biological chemistry 23 31201269
2018 Dual mTOR/PI3K inhibitor NVP‑BEZ235 arrests colorectal cancer cell growth and displays differential inhibition of 4E‑BP1. Oncology reports 23 29845289
2017 MicroRNA-138-5p controls sensitivity of nasopharyngeal carcinoma to radiation by targeting EIF4EBP1. Oncology reports 23 28075468
2014 4′,6-dihydroxy-4-methoxyisoaurone inhibits the HIF-1α pathway through inhibition of Akt/mTOR/p70S6K/4E-BP1 phosphorylation. Journal of pharmacological sciences 23 25075425
2009 Activated 4E-BP1 represses tumourigenesis and IGF-I-mediated activation of the eIF4F complex in mesothelioma. British journal of cancer 23 19603014
2003 Ser-64 and Ser-111 in PHAS-I are dispensable for insulin-stimulated dissociation from eIF4E. The Journal of biological chemistry 23 14507920
2014 GABARBP down-regulates HIF-1α expression through the VEGFR-2 and PI3K/mTOR/4E-BP1 pathways. Cellular signalling 21 24686084

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