Affinage

EIF4EBP1

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

Length
118 aa
Mass
12.6 kDa
Annotated
2026-04-28
100 papers in source corpus 48 papers cited in narrative 48 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EIF4EBP1 (4E-BP1) is an intrinsically disordered translational repressor that, in its hypophosphorylated state, binds eIF4E via a canonical YXXXXLΦ motif and an adjacent secondary interface to block assembly of the eIF4F cap-dependent translation initiation complex (PMID:7939721, PMID:26170285). mTORC1, scaffolded by Raptor through dual RAIP- and TOS-motif tethering, hierarchically phosphorylates 4E-BP1—first at Thr37/46 as a priming event, then at Thr70 and Ser65—inducing a disorder-to-order conformational switch that releases eIF4E; additional kinases including CDK12 (Ser65/Thr70), CDK1, p38/MSK1, and PLK1 and the phosphatase PP2A further tune 4E-BP1 phosphorylation in context-dependent ways (PMID:10364159, PMID:33852892, PMID:30819820, PMID:11777913, PMID:26199279). Transcriptional control of 4E-BP1 by ATF4 (ER stress), Smad4/TGFβ (growth arrest), and Snail (repression), together with post-translational regulation by O-GlcNAcylation-dependent stabilization opposing CUL3-mediated proteasomal degradation, adjusts 4E-BP1 protein levels to match cellular demand (PMID:18316032, PMID:19834456, PMID:29263324, PMID:26998719). Beyond translational control, 4E-BP1 regulates adipose tissue metabolism through PGC-1α translation, maintains mitochondrial complex III integrity to prevent senescence, supports oocyte meiotic spindle assembly, modulates circadian VIP expression in the SCN, and mediates cardiac survival downstream of mTORC1 (PMID:11590436, PMID:36929036, PMID:23852387, PMID:23972597, PMID:20644257).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1994 High

    Identification of 4E-BP1 as a direct eIF4E-binding protein whose phosphorylation by MAP kinase disrupts this interaction established the paradigm that cap-dependent translation is regulated by a phosphorylation-sensitive repressor.

    Evidence In vitro binding assays with immobilized PHAS-I and cap-affinity chromatography; molecular cloning revealing a 117-aa heat-stable, insulin-responsive protein

    PMID:7939721 PMID:8170978

    Open questions at the time
    • Identity of the physiological kinase in cells was unclear
    • Phosphorylation sites not yet mapped comprehensively
    • Mechanism by which phosphorylation disrupts binding was unknown
  2. 1997 High

    Demonstration that mTOR directly phosphorylates 4E-BP1 and that rapamycin blocks this phosphorylation placed 4E-BP1 as a direct mTOR substrate and explained rapamycin's translational effects.

    Evidence In vitro kinase assays with immunoprecipitated mTOR; rapamycin-resistant mTOR mutants protecting 4E-BP1 phosphorylation; phosphopeptide mapping identifying five Ser/Thr-Pro sites in rat adipocytes

    PMID:8599949 PMID:9092573 PMID:9204908 PMID:9334222

    Open questions at the time
    • Ordered hierarchy of phosphorylation events not yet resolved
    • Role of individual sites in eIF4E release unclear
    • Heat-shock-induced dephosphorylation mechanism (phosphatase identity) undefined
  3. 1999 High

    Reconstitution of mTOR-mediated phosphorylation revealed that Thr37/46 are priming sites whose modification is required for subsequent phosphorylation at C-terminal sites, establishing the hierarchical phosphorylation model.

    Evidence In vitro FRAP kinase assay with recombinant 4E-BP1, mass spectrometry phosphosite identification, site-directed mutagenesis showing loss of downstream phosphorylation upon Thr37/46 mutation

    PMID:10364159

    Open questions at the time
    • Structural basis for how priming enables downstream phosphorylation unknown
    • Whether hierarchy operates identically in vivo across tissues untested
  4. 2000 High

    Biophysical and kinase studies refined the ordered phosphorylation model and showed that phosphorylation weakens eIF4E binding regardless of cap status, but cannot dissociate preformed complexes, implying regulation occurs at the level of free 4E-BP1.

    Evidence Surface plasmon resonance quantifying ~100-fold cap-enhanced binding; in vitro mTOR kinase assay with activating antibody confirming Ser64 as most rapamycin-sensitive site

    PMID:10772338 PMID:10942774

    Open questions at the time
    • Structural mechanism of phosphorylation-induced conformational change unresolved
    • In vivo dynamics of complex formation/dissociation not measured
  5. 2001 High

    4E-BP1 knockout mice revealed unexpected metabolic functions—reduced white adipose tissue with browning and increased PGC-1α translation—demonstrating that 4E-BP1's translational repression has systemic physiological consequences beyond cell-autonomous growth control.

    Evidence Eif4ebp1−/− mice with histology, metabolic rate measurement, and polysome analysis in white adipose tissue

    PMID:11590436

    Open questions at the time
    • Contribution of 4E-BP2/3 compensation unclear
    • Tissue-specific mRNA targets beyond PGC-1α not identified
    • Mechanism linking translational changes to adipocyte fate unknown
  6. 2002 High

    Discovery that p38/MSK1 phosphorylates 4E-BP1 upon UVB irradiation independently of PI3K/Akt, and that non-phosphorylatable 4E-BP1 is proapoptotic through maximal cap-dependent translational repression, revealed mTOR-independent regulation and linked 4E-BP1 to apoptosis.

    Evidence Dominant-negative p38/MSK1 blocking UVB-induced phosphorylation; systematic phosphorylation-site mutants with apoptosis and dual-luciferase translation reporters

    PMID:11777913 PMID:11909977

    Open questions at the time
    • Whether MSK1 directly phosphorylates 4E-BP1 or acts through intermediary not definitively resolved
    • Apoptotic target mRNAs not identified
  7. 2003 High

    Identification of the RAIP and TOS motifs as dual Raptor-binding elements explained how mTORC1 selectively recognizes 4E-BP1 and established Raptor as a scaffold essential for efficient substrate phosphorylation.

    Evidence In vitro mTOR kinase assays with RAIP/TOS motif mutants, Raptor co-immunoprecipitation, cell size measurements upon TOS mutation

    PMID:12665511 PMID:12747827

    Open questions at the time
    • Structural basis for dual-motif recognition unknown
    • Relative contribution of each motif to phosphorylation hierarchy unresolved
  8. 2008 High

    ATF4-dependent transcriptional induction of 4E-BP1 under ER stress, and the finding that SF2/ASF orchestrates mTOR and PP2A to regulate 4E-BP1 phosphorylation on specific mRNAs, demonstrated that 4E-BP1 is regulated at both transcriptional and phosphatase levels to tune translation in stress contexts.

    Evidence ChIP confirming ATF4 binding to the 4E-BP1 promoter; Eif4ebp1−/− beta cells showing ER stress sensitivity; SF2/ASF co-IP with mTOR and PP2A

    PMID:18316032 PMID:18439897

    Open questions at the time
    • Full spectrum of 4E-BP1 transcriptional regulators undefined
    • PP2A regulatory subunit specificity for 4E-BP1 not identified
  9. 2010 High

    Cardiac-specific mTOR ablation causing lethal cardiomyopathy rescued by 4E-BP1 co-deletion, convergence of AKT and ERK pathways on 4E-BP1 phosphorylation in tumors, and biophysical demonstration that Ser65 phosphorylation destabilizes the α-helical binding conformation collectively established 4E-BP1 as a critical integration node whose conformational switch determines cell fate outcomes.

    Evidence Conditional cardiac mTOR/4E-BP1 double KO with echocardiography and survival; siRNA/inhibitor combinations with polysome profiling in cancer cells; ITC, CD, NMR, and computational modeling of phosphorylation-induced disorder

    PMID:20609351 PMID:20644257 PMID:20880835

    Open questions at the time
    • In vivo structural dynamics of phosphorylation-induced release from eIF4E not captured
    • Whether ERK directly or indirectly phosphorylates 4E-BP1 unresolved
  10. 2012 Medium

    PLK1 was identified as a mitotic kinase that directly phosphorylates and interacts with 4E-BP1 at centrosomes, linking 4E-BP1 to spindle integrity beyond its role in translation—a first indication of a non-canonical function.

    Evidence Co-immunoprecipitation and immunofluorescence co-localization with PLK1; in vitro PLK1 kinase assay; 4E-BP1 depletion causing multipolar spindles and polyploidy

    PMID:22918237

    Open questions at the time
    • PLK1-specific phosphosites on 4E-BP1 not mapped
    • Whether the spindle function is translation-dependent or translation-independent not established
    • Single-lab finding not independently confirmed
  11. 2013 High

    4E-BP1 was shown to preferentially repress VIP translation in the SCN to regulate circadian re-entrainment, and O-GlcNAcylation was discovered to enhance eIF4E binding and shift translation mode under hyperglycemia, expanding both the physiological and post-translational regulatory dimensions of 4E-BP1.

    Evidence Eif4ebp1−/− mice with circadian behavioral analysis and VIP immunoassay; KO cells with bicistronic reporters and SILAC proteomics under high glucose

    PMID:23434932 PMID:23972597

    Open questions at the time
    • Mechanism of mRNA-selective repression (VIP vs. other SCN transcripts) not defined
    • O-GlcNAcylation sites on 4E-BP1 not fully mapped
  12. 2015 High

    The 2.1-Å crystal structure of the eIF4E–4E-BP1 complex revealed a bipartite binding interface including a secondary helix containing Ser65/Thr70, providing the first atomic explanation of how phosphorylation at these sites would sterically and conformationally disrupt binding; enhanced 4E-BP1 in skeletal muscle was shown to protect against metabolic decline via PGC-1α and FGF21.

    Evidence X-ray crystallography with functional validation by truncation mutants and cell cycle assays; muscle-specific 4E-BP1 transgenic mice with metabolic, translation, and adipose phenotyping

    PMID:26121750 PMID:26170285

    Open questions at the time
    • Full-length 4E-BP1 structure in complex with eIF4E lacking
    • How FGF21 secretion is translationally controlled by 4E-BP1 unclear
  13. 2017 High

    Snail was identified as a transcriptional repressor of 4E-BP1 via E-box elements, providing a mechanism by which EMT programs bypass mTOR-targeted therapy; CDK1 and mTOR (but not PLK1) were confirmed as the dominant kinases for 4E-BP1 during oocyte meiotic resumption.

    Evidence ChIP of Snail on 4E-BP1 promoter, polysome profiling, xenograft sensitivity; pharmacological epistasis in mouse and human oocytes with dominant-negative 4E-BP1

    PMID:28272965 PMID:29263324

    Open questions at the time
    • Whether Snail-mediated 4E-BP1 repression operates outside cancer contexts unknown
    • Direct CDK1 phosphosites on 4E-BP1 during meiosis not mapped
  14. 2018 High

    The lncRNA H19 was found to bind the TOS motif of 4E-BP1 and competitively inhibit Raptor interaction, revealing an RNA-based mechanism that selectively modulates 4E-BP1 phosphorylation without affecting S6K1.

    Evidence RNA immunoprecipitation, protein co-IP demonstrating competition between H19 and Raptor for TOS motif binding

    PMID:30397197

    Open questions at the time
    • Whether other lncRNAs similarly regulate 4E-BP1 unknown
    • Physiological contexts where H19-mediated regulation is dominant not established
  15. 2019 High

    CDK12 was identified as a kinase phosphorylating 4E-BP1 at Ser65/Thr70 after mTORC1 priming, controlling the translational switch from 4E-BP1 to eIF4G on CHK1 and other target mRNAs; O-GlcNAcylation was shown to stabilize 4E-BP1 by blocking CUL3-mediated PEST-motif ubiquitination; genome-wide profiling revealed 4E-BP1-dependent selective translation of DNA replication/repair mRNAs.

    Evidence In vitro CDK12 kinase assay with RIP-seq and Ribo-seq; PEST mutagenesis with CUL3 co-IP and ubiquitination assays; polysome profiling in 4E-BP1-depleted pancreatic cancer cells and KO mice

    PMID:26998719 PMID:30819820 PMID:31672935

    Open questions at the time
    • CDK12 substrate specificity relative to other CDKs on 4E-BP1 not fully resolved
    • Full set of 4E-BP1-sensitive mRNAs across tissues not catalogued
    • CUL3 adaptor subunit mediating 4E-BP1 recognition not identified
  16. 2021 High

    NMR-resolved mapping of the 4E-BP1–Raptor interface showed that RAIP and TOS motifs bind separate Raptor surfaces, creating avidity-based tethering that orients the flexible central domain toward the mTORC1 active site, providing the structural explanation for hierarchical phosphorylation.

    Evidence NMR spectroscopy of 4E-BP1 interaction with Raptor, mutagenesis, and in vitro mTORC1 kinase assays

    PMID:33852892

    Open questions at the time
    • Cryo-EM structure of the full mTORC1–4E-BP1 complex not yet available
    • How phosphorylation at Thr37/46 repositions the substrate for subsequent kinase events at atomic resolution unresolved
  17. 2023 High

    4E-BP1 was shown to sustain mitochondrial complex III integrity by promoting translation of UQCRC2 and related subunits; its loss in human MSCs elevated ROS and accelerated senescence, rescued by ectopic 4E-BP1 expression.

    Evidence CRISPR KO in hMSCs with ectopic rescue, mitochondrial respiration assays, complex III subunit quantification

    PMID:36929036

    Open questions at the time
    • Whether 4E-BP1 directly binds mitochondrial mRNAs or acts through general cap-dependent control of nuclear-encoded subunits is unresolved
    • Relevance to in vivo aging not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full structural basis of the mTORC1–4E-BP1 complex at atomic resolution, the complete inventory of 4E-BP1-sensitive mRNAs across tissues, the identity of the CUL3 adaptor for 4E-BP1 ubiquitination, and whether the centrosomal/spindle functions of 4E-BP1 are translation-independent.
  • No high-resolution cryo-EM structure of mTORC1 engaged with full-length 4E-BP1
  • Translation-independent spindle role not mechanistically separated from local translation
  • Tissue-specific 4E-BP1-regulated translatomes largely unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0060090 molecular adaptor activity 4
Localization
GO:0005829 cytosol 3 GO:0005815 microtubule organizing center 2 GO:0005856 cytoskeleton 2
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-392499 Metabolism of proteins 6 R-HSA-1640170 Cell Cycle 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-1430728 Metabolism 3 R-HSA-5357801 Programmed Cell Death 2
Partners
CDK12CDKN1ACUL3EIF4EMTORPLK1PP2ARPTOR
Complex memberships
eIF4E–4E-BP1 inhibitory complex

Evidence

Reading pass · 48 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 Non-phosphorylated 4E-BP1 (PHAS-I) binds directly to eIF4E and inhibits cap-dependent translation; MAP kinase phosphorylates Ser-64 of 4E-BP1, which disrupts the 4E-BP1/eIF4E interaction and relieves translational repression. In vitro binding assays, immobilized PHAS-I pulldown, mRNA cap affinity resin, in vitro phosphorylation by MAP kinase Science High 7939721
1994 4E-BP1 (PHAS-I) is a 117 amino acid heat-stable protein that is rapidly phosphorylated in response to insulin and is expressed at highest levels in fat and skeletal muscle. Molecular cloning, in vitro translation, tissue expression analysis Proceedings of the National Academy of Sciences of the United States of America High 8170978
1996 Rapamycin blocks 4E-BP1 phosphorylation, activating 4E-BP1 and causing inhibition of cap-dependent (but not cap-independent) translation; the rapamycin-FKBP12 complex is the effector, and excess FK506 reverses this inhibition. In vitro translation assays, pharmacological inhibition in NIH 3T3 cells, polysome analysis The EMBO journal High 8599949
1997 mTOR (FRAP) directly phosphorylates 4E-BP1 (PHAS-I) on serine and threonine residues in vitro, and this phosphorylation inhibits binding of 4E-BP1 to eIF4E; mTOR is a terminal kinase in the pathway coupling mitogenic stimulation to 4E-BP1 phosphorylation. In vitro kinase assays with immunoprecipitated mTOR, cell-based phosphorylation studies with rapamycin-sensitive mTOR mutants Science High 9204908
1997 mTOR regulates 4E-BP1 and p70 S6 kinase in a parallel (not sequential) manner; rapamycin-resistant mTOR mutants protect both 4E-BP1 and S6K from rapamycin-induced dephosphorylation, and this protection requires an active mTOR catalytic domain. Expression of rapamycin-resistant mTOR mutants, in situ phosphorylation assays The Journal of biological chemistry High 9334222
1997 In rat adipocytes, insulin stimulates phosphorylation of 4E-BP1 at Thr36, Thr45, Ser64, Thr69, and Ser82 (all Ser/Thr-Pro motifs), and all five sites are decreased by rapamycin; phosphorylation of Thr36 alone is insufficient for dissociation of the 4E-BP1/eIF4E complex. Phosphopeptide mapping by reverse-phase HPLC and Edman degradation, in vitro MAP kinase phosphorylation, cell-based studies with rapamycin The Journal of biological chemistry High 9092573
1997 Heat shock causes dephosphorylation of 4E-BP1 in H35 hepatoma cells and other cell lines, which is accompanied by increased eIF4E binding to 4E-BP1 and inhibition of translation; this dephosphorylation is reversed by the phosphatase inhibitor okadaic acid. Phosphorylation analysis by gel shift, eIF4E pulldown, phosphatase inhibitor treatment The Journal of biological chemistry Medium 9341116
1998 4E-BP1 is completely disordered in its free state (no regions of local order detectable by NMR), indicating that its binding to eIF4E is an induced-fit interaction with a completely disordered protein. NMR spectroscopy (double and triple resonance, steady-state NOEs) Protein science High 9684899
1999 mTOR/FRAP phosphorylates 4E-BP1 on Thr-37 and Thr-46 in vitro (even when 4E-BP1 is bound to eIF4E), and these phosphorylations serve as a priming event required for subsequent phosphorylation of carboxy-terminal serum-sensitive sites; loss of these priming sites prevents downstream multi-site phosphorylation. In vitro kinase assays with recombinant FRAP, phosphopeptide mapping, mass spectrometry, site-directed mutagenesis Genes & development High 10364159
1999 4E-BP1 exists as 8-10 phosphorylation isoforms resolvable by 2D gel electrophoresis; heat shock induces rapid dephosphorylation of 4E-BP1 concurrent with translation inhibition, and phosphatase inhibitor okadaic acid restores phosphorylation during heat shock. 2D IEF/SDS-PAGE immunoblotting, [32P] metabolic labeling, okadaic acid treatment European journal of biochemistry Medium 10504405
2000 mTOR directly phosphorylates 4E-BP1 at Thr-36/45 and (with an activating antibody) at Thr-69 and Ser-64 in vitro; phosphorylation of Thr-36/45 by mTOR facilitates subsequent Thr-69 and Ser-64 phosphorylation in an ordered hierarchy; phosphorylation of Ser-64 is most rapamycin-sensitive. In vitro kinase assay with immunoprecipitated mTOR, phospho-specific antibodies, rapamycin-FKBP12 inhibition The Journal of biological chemistry High 10942774
2000 Cap-dependent binding of 4E-BP1 to eIF4E is enhanced ~100-fold in the presence of m7GTP; phosphorylation of 4E-BP1 weakens interaction with eIF4E regardless of cap status, and pre-formed 4E-BP1/eIF4E complexes are not dissociated by phosphorylation, suggesting regulation occurs at the free 4E-BP1 state. Surface plasmon resonance binding analysis IUBMB life Medium 10772338
2001 4E-BP1 knockout mice have markedly smaller white fat pads; knockout males display increased metabolic rate and white adipose tissue containing multilocular brown-adipocyte-like cells expressing UCP1; translation of PGC-1α is increased in white adipose tissue of knockout mice, demonstrating 4E-BP1 as a regulator of adipogenesis and metabolism. Gene knockout in mice (Eif4ebp1-/-), histology, metabolic rate measurement, Western blotting, polysome analysis Nature medicine High 11590436
2001 During liver regeneration after partial hepatectomy in rats, 4E-BP1 phosphorylation is induced in a rapamycin-insensitive manner, demonstrating that mTOR-independent kinases can phosphorylate 4E-BP1 in vivo. Partial hepatectomy rat model, phospho-specific antibodies, rapamycin treatment The Journal of biological chemistry Medium 11278364
2002 Phosphorylation events govern the proapoptotic potency of 4E-BP1; phosphorylation site mutants of 4E-BP1 that more strongly repress cap-dependent translation are more potently proapoptotic; at maximum translational repression, cap-independent (IRES-dependent) translation is activated, reducing apoptosis. Expression of phosphorylation site mutants, cap-dependent vs. IRES-dependent translation reporters, apoptosis assays Molecular and cellular biology High 11909977
2003 Both the N-terminal RAIP motif and C-terminal TOS motif of 4E-BP1 are required for efficient in vitro phosphorylation by mTOR and for binding to Raptor; raptor overexpression enhances phosphorylation of wild-type but not motif-mutant 4E-BP1, indicating Raptor serves as a docking scaffold for 4E-BP1 phosphorylation by mTOR. In vitro mTOR kinase assay with recombinant PHAS-I mutants, co-immunoprecipitation with HA-tagged raptor, mutagenesis The Journal of biological chemistry High 12665511
2003 A functional TOS motif in 4E-BP1 is required for binding to Raptor, for efficient in vitro phosphorylation by mTOR/Raptor complex, and for phosphorylation at all mTOR-regulated sites in vivo; TOS motif mutation (F114A) causes reduced cell size, demonstrating TOS-dependent mTOR/Raptor-mediated regulation of cell growth. Co-immunoprecipitation, in vitro mTOR/raptor kinase assay, site-directed mutagenesis, cell size measurement Current biology High 12747827
2003 Ser-64 and Ser-111 are not required for insulin-stimulated dissociation of 4E-BP1 from eIF4E; Thr-36/45 phosphorylation is implicated as the primary determinant of 4E-BP1/eIF4E dissociation. Mutagenesis (Ala-64 and Ala-111 mutants), in situ phosphorylation analysis, eIF4E binding assay The Journal of biological chemistry High 14507920
2004 4E-BP1 binds to the eIF4E homologous protein 4EHP via its canonical eIF4E-binding motif (Y54 and L59 required); 4EHP overexpression creates a negative feedback loop inhibiting upstream signaling to 4E-BP1 and S6K1, and this feedback requires the 4E-BP1-binding capability of 4EHP. Co-immunoprecipitation, site-directed mutagenesis of 4E-BP1 and 4EHP binding interfaces FEBS letters Medium 15094042
2008 SR protein SF2/ASF promotes translation initiation of bound mRNAs by suppressing 4E-BP1 activity; SF2/ASF interacts with both mTOR and the phosphatase PP2A to regulate 4E-BP1 phosphorylation, functioning as an adaptor to recruit translation regulatory molecules to specific mRNAs. Co-immunoprecipitation, translation reporter assays, mTOR/PP2A interaction studies Molecular cell High 18439897
2008 ATF4 directly transcriptionally induces 4E-BP1 expression under ER stress; elevated 4E-BP1 in pancreatic beta cells under ER stress is required for cell survival; Eif4ebp1 deletion increases susceptibility to ER stress-mediated apoptosis and accelerates beta cell loss in diabetic mouse models. Chromatin IP, 4E-BP1 promoter-reporter assay, Eif4ebp1 knockout mouse, MIN6 beta cell knockdown, diabetic mouse models Cell metabolism High 18316032
2002 UVB irradiation induces 4E-BP1 phosphorylation at Thr-36, Thr-45, Ser-64, and Thr-69 via the p38/MSK1 pathway (not PI3K/Akt); dominant-negative p38 and MSK1 block UVB-induced 4E-BP1 phosphorylation and eIF4E release. Dominant-negative kinase expression, pharmacological inhibitors (p38 inhibitors, wortmannin, H89), in vivo phosphorylation assays The Journal of biological chemistry High 11777913
2009 4E-BP1 is a transcriptional target of Smad4; TGFβ-stimulated Smad4 enhances 4E-BP1 gene-promoter activity through a conserved Smad-binding element; 4E-BP1 is required for TGFβ-mediated antiproliferative effects. Smad4 ChIP, 4E-BP1 promoter-reporter assay, siRNA knockdown, 4E-BP1 knockout MEFs, Smad4+/+ vs Smad4-/- cell lines The EMBO journal High 19834456
2010 mTORC1 ablation in mouse myocardium causes fatal dilated cardiomyopathy with 4E-BP1 accumulation; simultaneous ablation of 4E-BP1 together with mTOR markedly improves cardiac apoptosis, heart function, and survival, demonstrating that 4E-BP1 mediates the deleterious effects of reduced mTOR activity in the heart. Cardiac-specific Mtor knockout mouse, double knockout of Mtor and Eif4ebp1, histology, echocardiography, survival analysis The Journal of clinical investigation High 20644257
2010 Non-phosphorylated 4E-BP1 interacts with p21 protein and induces its proteasomal degradation; mTORC1 activation phosphorylates 4E-BP1, preventing this p21-destabilizing interaction and thereby stabilizing p21 protein in HNSCC cells. Co-immunoprecipitation, Western blotting with phospho-4E-BP1 mutants, siRNA knockdown Nature communications Medium 26832959
2010 4E-BP1 and ERK pathways converge to regulate cap-dependent translation via 4E-BP1; both AKT and ERK pathways independently regulate 4E-BP1 phosphorylation, and their combined inhibition is required to fully suppress translation in tumors with co-activation of both pathways; knockdown of 4E-BP1 reduces dependence on AKT/ERK signaling. siRNA knockdown, dominant-active 4E-BP1 mutant, inhibitor combinations, polysome profiling Cancer cell High 20609351
2010 The disorder-to-order transition of 4E-BP1 is required for tight eIF4E binding; phosphorylation of S65 destabilizes the α-helical conformation of the 4E-BP1 binding motif, biasing the free energy landscape toward the unfolded state that cannot bind eIF4E. Isothermal calorimetry, circular dichroism, NMR, computational modeling Proceedings of the National Academy of Sciences of the United States of America High 20880835
2011 MCV small T antigen acts downstream of mTORC1 to maintain 4E-BP1 hyperphosphorylation and dysregulated cap-dependent translation; MCV sT-induced hyperphosphorylation of 4E-BP1 Ser65 is resistant to mTORC1/mTORC2 inhibitors; constitutively active non-phosphorylatable 4E-BP1 antagonizes MCV sT transformation. Dominant-active 4E-BP1 mutant expression, mTORC1/2 inhibitor treatment, cell transformation assays The Journal of clinical investigation High 21841310
2012 4E-BP1 co-localizes with PLK1 at centrosomes during mitosis; 4E-BP1 interacts directly 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, multi-polar spindles, and sensitizes cells to paclitaxel. Co-immunoprecipitation, in vitro kinase assay with PLK1, siRNA knockdown, immunofluorescence co-localization Cell cycle Medium 22918237
2012 Phosphorylation at Thr46 alone (rapamycin-insensitive) is sufficient to prevent eIF4E:4E-BP1 binding, establishing that the initial rapamycin-insensitive mTORC1 phosphorylation at Thr46 directly regulates the 4E-BP1/eIF4E interaction. Site-directed mutagenesis of 4E-BP1, eIF4E co-immunoprecipitation, rapamycin and mTOR kinase inhibitor treatment F1000Research Medium 24358826
2013 mTOR/4E-BP1 signaling in the suprachiasmatic nucleus (SCN) is rhythmically regulated; 4E-BP1 preferentially represses VIP mRNA translation; Eif4ebp1 knockout mice display accelerated re-entrainment to shifted light/dark cycles and are more resistant to constant light-induced rhythm disruption; Mtor+/- mice show decreased VIP expression and increased susceptibility to constant light. Eif4ebp1 knockout mouse, Mtor heterozygous mouse, VIP immunoassay, circadian behavior analysis, mTOR inhibitor treatment Neuron High 23972597
2013 O-GlcNAcylation of 4E-BP1 in hyperglycemic conditions enhances its interaction with eIF4E and causes a shift from cap-dependent to cap-independent mRNA translation; this glucose-induced translational shift does not occur in 4E-BP1-deficient cells. 4E-BP1 knockout cells, bicistronic luciferase reporter assay, pulsed SILAC proteomics, phlorizin treatment of STZ-diabetic mice Diabetes High 23434932
2013 Phosphorylated EIF4EBP1 localizes to the spindle apparatus in mouse oocytes during meiosis in a phosphorylation-site-specific manner: Ser65-phosphorylated 4E-BP1 localizes at spindle poles, Thr70-phosphorylated 4E-BP1 localizes on the spindle; CDK1 and mTOR are the main positive regulators after nuclear envelope breakdown; expression of dominant-negative 4E-BP1 causes spindle abnormality. Immunofluorescence, Western blotting, CDK1 and mTOR inhibitors, dominant-negative 4E-BP1 expression, mouse oocyte maturation model Genetics Medium 23852387
2015 The 2.1-Å crystal structure of mouse eIF4E complexed with m7GTP and a 4E-BP1 fragment (residues 50-84) reveals two binding motifs: the canonical YXXXXLΦ motif and a proline-turn-helix extension containing S65 and T70 phosphorylation sites; a C-terminal motif (motif 3) is critical for 4E-BP1-mediated cell cycle arrest and partially overlaps with the 4EGI-1 binding site. X-ray crystallography at 2.1 Å, cell cycle arrest assays with 4E-BP1 truncation mutants Proceedings of the National Academy of Sciences of the United States of America High 26170285
2015 Enhanced 4E-BP1 activity in mouse skeletal muscle protects against age- and diet-induced insulin resistance and metabolic decline; 4E-BP1-mediated metabolic protection occurs through increased translation of PGC-1α and enhanced mitochondrial respiratory function; skeletal muscle 4E-BP1 also promotes FGF21 secretion preserving brown adipose tissue. Muscle-specific 4E-BP1 transgenic mice, metabolic rate measurements, polysome/translation assays, adipose tissue phenotyping The Journal of clinical investigation High 26121750
2017 Snail transcriptionally represses 4E-BP1 by binding to three E-boxes in the human 4E-BP1 promoter; Snail overexpression promotes cap-dependent translation and reduces sensitivity to mTOR kinase inhibitors; pharmacological inhibition of Snail restores 4E-BP1 expression and sensitizes cancer cells to mTOR inhibitors. Chromatin IP, promoter-reporter assay, Snail overexpression and knockdown, polysome profiling, tumor xenograft Nature communications High 29263324
2017 In mouse oocytes, 4E-BP1 undergoes meiosis-resumption-dependent phosphorylation by CDK1 and mTOR (but not PLK1); CDK1 promotes 4E-BP1 phosphorylation via phosphorylation and activation of mTOR; dominant-negative 4E-BP1 impairs translation and causes spindle abnormalities; this mTOR regulatory pathway is also present in human oocytes. Immunofluorescence in mouse/human oocytes, CDK1/PLK1/mTOR inhibitors, dominant-negative 4E-BP1 expression, cumulus cell comparison Cell cycle High 28272965
2018 lncRNA H19 directly interacts with 4E-BP1 at its TOS motif and competitively inhibits 4E-BP1 binding to Raptor, thereby blocking mTORC1-mediated 4E-BP1 phosphorylation without affecting S6K1 activation. RNA immunoprecipitation, co-immunoprecipitation of H19/4E-BP1/Raptor, TOS motif competition assay, 4E-BP1 phosphorylation analysis Nature communications High 30397197
2019 CDK12 phosphorylates 4E-BP1 at S65 and T70 (Ser-Pro sites); prior mTORC1 phosphorylation at T37/T46 facilitates CDK12 phosphorylation; CDK12-dependent 4E-BP1 phosphorylation controls exchange of 4E-BP1 with eIF4G at the 5' cap of CHK1 and other target mRNAs; CDK12 depletion causes chromosome misalignment and segregation defects. In vitro CDK12 kinase assay, RIP-seq, Ribo-seq, confocal imaging, mutagenesis of phosphorylation sites Genes & development High 30819820
2019 rapamycin-insensitive mTORC1 signaling via 4E-BP1 (not canonical PI3K/Akt) is a critical pathway for TGF-β1-stimulated collagen synthesis in human lung fibroblasts; CRISPR-Cas9 deletion of 4E-BP1 confirms its essential role in fibrogenesis. CRISPR-Cas9 gene editing, mTOR inhibitors, collagen synthesis assays, precision-cut lung slices Nature communications High 30602778
2019 In HNSCC, mTOR persistently restrains 4E-BP1 via phosphorylation; CRISPR/Cas9 deletion of 4E-BP1 reduces sensitivity to mTOR inhibitors both in vitro and in vivo; conditional expression of phosphorylation-resistant 4E-BP1 disrupts the translation initiation complex and prevents tumor growth. CRISPR-Cas9 4E-BP1 deletion, conditional phosphorylation-resistant 4E-BP1 expression, 4e-bp1/2 knockout mouse carcinogenesis models, tumor xenograft Cancer research High 30894372
2019 O-GlcNAcylation of 4E-BP1 stabilizes it by slowing degradation via its PEST motif; a CUL3-containing E3 ubiquitin ligase complex binds the PEST motif to mediate 4E-BP1 polyubiquitination and turnover; O-GlcNAcylation of the PEST motif prevents this ubiquitination, increasing 4E-BP1 protein levels in diabetic retinas. PEST motif mutagenesis, CUL3 co-immunoprecipitation, ubiquitination assays, O-GlcNAcase inhibitor treatment, pulse-chase degradation assay Investigative ophthalmology & visual science High 26998719
2021 By NMR spectroscopy, the N-terminal RAIP motif and C-terminal TOS motif of 4E-BP1 bind to separate sites on Raptor, creating avidity-based tethering; this dual tethering orients the flexible central region toward the mTORC1 kinase site; phosphorylation-induced conformational switching of 4E-BP1 explains the hierarchy of phosphorylation; mTORC1 recognizes both free and eIF4E-bound 4E-BP1. NMR spectroscopy of 4E-BP1 interaction with Raptor, mutagenesis, in vitro mTORC1 kinase assays Molecular cell High 33852892
2008 p53 activation leads to proteasome-mediated truncation of 4E-BP1, producing a stable, hypophosphorylated, truncated form that binds eIF4E preferentially over full-length 4E-BP1, contributing to long-term inhibition of cap-dependent translation. Proteasome inhibitor treatment, co-immunoprecipitation, pulse-chase turnover assay, p53 activation Biology of the cell Medium 18021075
2009 RhoE inhibits 4E-BP1 phosphorylation independently of mTOR (as S6K phosphorylation and mTOR/Raptor dynamics are unaffected), preventing eIF4E release from 4E-BP1 and inhibiting cap-dependent translation; eIF4E overexpression rescues both cell cycle progression and Ras-induced transformation in RhoE-expressing cells. RhoE overexpression, pharmacological comparisons with rapamycin, eIF4E rescue, translation reporter assays The Journal of biological chemistry Medium 19850923
2015 PP2A-mediated dephosphorylation of 4E-BP1 is the dominant mechanism controlling 4E-BP1 phosphorylation status in the retina in response to inhibition of glycolysis; glycolytic inhibition dephosphorylates 4E-BP1 independently of mTORC1 through phosphatase activation. Ex vivo rat retina preparations, phosphatase inhibitors (okadaic acid, calyculin A, cadmium), 2-deoxyglucose, mTORC1 activity assays American journal of physiology. Endocrinology and metabolism Medium 26199279
2019 4E-BP1 loss in pancreatic cancer cells leads to selective upregulation of translation of mRNAs encoding DNA replication/repair proteins (including RRM2 and CDC6), making DNA replication insensitive to mTOR inhibitors; this effect is confirmed in 4E-BP1/2-deleted mice showing increased acinar proliferation after pancreatitis. Genome-wide polysome profiling, 4E-BP1 depletion, 4E-BP1/2 double-knockout mouse, eIF4A inhibitor treatment JCI insight High 31672935
2023 4E-BP1 stabilizes mitochondrial respiration complex III proteins (including UQCRC2) at the translational level; 4E-BP1 deficiency in human MSCs destabilizes complex III subunits, increases mitochondrial ROS, and accelerates cellular senescence; ectopic 4E-BP1 expression rescues these mitochondrial defects. 4E-BP1 gene inactivation by CRISPR in hMSCs, ectopic expression rescue, Western blotting of respiratory complex subunits, mitochondrial respiration assays, ROS measurement Protein & cell High 36929036

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 1096 10364159
1997 Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin. Science (New York, N.Y.) 813 9204908
1994 PHAS-I as a link between mitogen-activated protein kinase and translation initiation. Science (New York, N.Y.) 616 7939721
1996 Rapamycin blocks the phosphorylation of 4E-BP1 and inhibits cap-dependent initiation of translation. The EMBO journal 575 8599949
1997 Regulation of eIF-4E BP1 phosphorylation by mTOR. The Journal of biological chemistry 412 9334222
2003 TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function. Current biology : CB 399 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 347 20609351
2001 Adipose tissue reduction in mice lacking the translational inhibitor 4E-BP1. Nature medicine 311 11590436
2011 Human Merkel cell polyomavirus small T antigen is an oncoprotein targeting the 4E-BP1 translation regulator. The Journal of clinical investigation 295 21841310
2010 MTORC1 regulates cardiac function and myocyte survival through 4E-BP1 inhibition in mice. The Journal of clinical investigation 291 20644257
2004 Activation of the Akt/mammalian target of rapamycin/4E-BP1 pathway by ErbB2 overexpression predicts tumor progression in breast cancers. Clinical cancer research : an official journal of the American Association for Cancer Research 267 15501954
2016 4E-BP1, a multifactor regulated multifunctional protein. Cell cycle (Georgetown, Tex.) 256 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
2008 The splicing factor SF2/ASF regulates translation initiation by enhancing phosphorylation of 4E-BP1. Molecular cell 226 18439897
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 198 8643618
1997 Identification of phosphorylation sites in the translational regulator, PHAS-I, that are controlled by insulin and rapamycin in rat adipocytes. The Journal of biological chemistry 168 9092573
2019 The mTORC1/4E-BP1 axis represents a critical signaling node during fibrogenesis. Nature communications 167 30602778
2008 ATF4-mediated induction of 4E-BP1 contributes to pancreatic beta cell survival under endoplasmic reticulum stress. Cell metabolism 159 18316032
2016 Eukaryotic initiation factor 4E-binding protein 1 (4E-BP1): a master regulator of mRNA translation involved in tumorigenesis. Oncogene 144 26829052
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 123 23972597
2000 Mammalian target of rapamycin-dependent phosphorylation of PHAS-I in four (S/T)P sites detected by phospho-specific antibodies. The Journal of biological chemistry 115 10942774
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
1998 Amino acid effects on translational repressor 4E-BP1 are mediated primarily by L-leucine in isolated adipocytes. The American journal of physiology 111 9814971
2018 Inhibition of mTORC1 by lncRNA H19 via disrupting 4E-BP1/Raptor interaction in pituitary tumours. Nature communications 105 30397197
2015 Muscle-specific 4E-BP1 signaling activation improves metabolic parameters during aging and obesity. The Journal of clinical investigation 102 26121750
2011 High-dose rapamycin induces apoptosis in human cancer cells by dissociating mTOR complex 1 and suppressing phosphorylation of 4E-BP1. Cell cycle (Georgetown, Tex.) 96 22071574
2002 Signal pathways involved in activation of p70S6K and phosphorylation of 4E-BP1 following exposure of multiple myeloma tumor cells to interleukin-6. The Journal of biological chemistry 95 11872747
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
2015 Molecular mechanism of the dual activity of 4EGI-1: Dissociating eIF4G from eIF4E but stabilizing the binding of unphosphorylated 4E-BP1. Proceedings of the National Academy of Sciences of the United States of America 93 26170285
2008 CCL5-mediated T-cell chemotaxis involves the initiation of mRNA translation through mTOR/4E-BP1. Blood 93 18337562
2002 Translational control of cell fate: availability of phosphorylation sites on translational repressor 4E-BP1 governs its proapoptotic potency. Molecular and cellular biology 89 11909977
2013 Arginine, leucine, and glutamine stimulate proliferation of porcine trophectoderm cells through the MTOR-RPS6K-RPS6-EIF4EBP1 signal transduction pathway. Biology of reproduction 88 23486913
2003 Alcohol impairs leucine-mediated phosphorylation of 4E-BP1, S6K1, eIF4G, and mTOR in skeletal muscle. American journal of physiology. Endocrinology and metabolism 86 12944322
2012 PTEN/Akt signaling controls mitochondrial respiratory capacity through 4E-BP1. PloS one 84 23049865
2015 mTOR inhibitors induce apoptosis in colon cancer cells via CHOP-dependent DR5 induction on 4E-BP1 dephosphorylation. Oncogene 81 25867072
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
2013 Incomplete inhibition of phosphorylation of 4E-BP1 as a mechanism of primary resistance to ATP-competitive mTOR inhibitors. Oncogene 77 23542178
2001 Rapamycin-insensitive regulation of 4e-BP1 in regenerating rat liver. The Journal of biological chemistry 76 11278364
2012 mTOR-independent 4E-BP1 phosphorylation is associated with cancer resistance to mTOR kinase inhibitors. Cell cycle (Georgetown, Tex.) 70 22262166
2021 The dynamic mechanism of 4E-BP1 recognition and phosphorylation by mTORC1. Molecular cell 69 33852892
1998 The interaction of eIF4E with 4E-BP1 is an induced fit to a completely disordered protein. Protein science : a publication of the Protein Society 69 9684899
2019 CDK12 phosphorylates 4E-BP1 to enable mTORC1-dependent translation and mitotic genome stability. Genes & development 68 30819820
2019 4E-BP1 Is a Tumor Suppressor Protein Reactivated by mTOR Inhibition in Head and Neck Cancer. Cancer research 65 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 55 23563181
2016 MicroRNAs 125a and 125b inhibit ovarian cancer cells through post-transcriptional inactivation of EIF4EBP1. Oncotarget 53 26646586
2004 Inhibition of insulin signaling and adipogenesis by rapamycin: effect on phosphorylation of p70 S6 kinase vs eIF4E-BP1. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity 53 14970836
2010 Suppression of hypoxia-inducible factor 1α (HIF-1α) by tirapazamine is dependent on eIF2α phosphorylation rather than the mTORC1/4E-BP1 pathway. PloS one 51 21085474
2009 4E-BP1 is a target of Smad4 essential for TGFbeta-mediated inhibition of cell proliferation. The EMBO journal 49 19834456
1997 Inactivation of eIF2B and phosphorylation of PHAS-I in heat-shocked rat hepatoma cells. The Journal of biological chemistry 48 9341116
2015 AKT inhibition overcomes rapamycin resistance by enhancing the repressive function of PRAS40 on mTORC1/4E-BP1 axis. Oncotarget 47 25961827
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 45 34740159
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
2006 Deregulation of eIF4E: 4E-BP1 in differentiated human papillomavirus-containing cells leads to high levels of expression of the E7 oncoprotein. Journal of virology 45 16809313
2016 Stabilization of p21 by mTORC1/4E-BP1 predicts clinical outcome of head and neck cancers. Nature communications 42 26832959
2019 ANGPTL4 Induces TMZ Resistance of Glioblastoma by Promoting Cancer Stemness Enrichment via the EGFR/AKT/4E-BP1 Cascade. International journal of molecular sciences 40 31717924
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
2007 Phenethyl isothiocyanate, a cancer chemopreventive constituent of cruciferous vegetables, inhibits cap-dependent translation by regulating the level and phosphorylation of 4E-BP1. Cancer research 38 17440067
2017 Regulation of 4E-BP1 activity in the mammalian oocyte. Cell cycle (Georgetown, Tex.) 37 28272965
2014 Loss of PINK1 attenuates HIF-1α induction by preventing 4E-BP1-dependent switch in protein translation under hypoxia. The Journal of neuroscience : the official journal of the Society for Neuroscience 37 24553947
2010 Local control of a disorder-order transition in 4E-BP1 underpins regulation of translation via eIF4E. Proceedings of the National Academy of Sciences of the United States of America 36 20880835
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
2009 Inhibition of mammalian target of rapamycin (mTOR) signalling in C2C12 myoblasts prevents myogenic differentiation without affecting the hyperphosphorylation of 4E-BP1. Cellular signalling 34 19481146
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
2022 The mTOR/4E-BP1/eIF4E Signalling Pathway as a Source of Cancer Drug Targets. Current medicinal chemistry 33 35209811
2017 Luteolin, a natural flavonoid, inhibits methylglyoxal induced apoptosis via the mTOR/4E-BP1 signaling pathway. Scientific reports 33 28801605
2017 Snail determines the therapeutic response to mTOR kinase inhibitors by transcriptional repression of 4E-BP1. Nature communications 32 29263324
2013 Hyperglycemia mediates a shift from cap-dependent to cap-independent translation via a 4E-BP1-dependent mechanism. Diabetes 32 23434932
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
2012 Rapamycin-insensitive mTORC1 activity controls eIF4E:4E-BP1 binding. F1000Research 31 24358826
1997 Disruption of the gene encoding the mitogen-regulated translational modulator PHAS-I in mice. The Journal of biological chemistry 31 9395487
2023 4E-BP1 counteracts human mesenchymal stem cell senescence via maintaining mitochondrial homeostasis. Protein & cell 30 36929036
2012 Nanosecond pulsed electric fields act as a novel cellular stress that induces translational suppression accompanied by eIF2α phosphorylation and 4E-BP1 dephosphorylation. Experimental cell research 30 22652449
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
2000 Regulation of human eIF4E by 4E-BP1: binding analysis using surface plasmon resonance. IUBMB life 29 10772338
2016 The Translational Repressor 4E-BP1 Contributes to Diabetes-Induced Visual Dysfunction. Investigative ophthalmology & visual science 28 26998719
2008 Activation of p53 stimulates proteasome-dependent truncation of eIF4E-binding protein 1 (4E-BP1). Biology of the cell 28 18021075
2008 Phosphatidylinositol 3-kinase-dependent transcriptional silencing of the translational repressor 4E-BP1. Cellular and molecular life sciences : CMLS 28 18810319
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
2010 Modulation of 4E-BP1 function as a critical determinant of enzastaurin-induced apoptosis. Molecular cancer therapeutics 26 20971826
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
2015 Phosphatase control of 4E-BP1 phosphorylation state is central for glycolytic regulation of retinal protein synthesis. American journal of physiology. Endocrinology and metabolism 25 26199279
2019 4E-BP1 and 4E-BP2 double knockout mice are protected from aging-associated sarcopenia. Journal of cachexia, sarcopenia and muscle 23 30927336
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 Overexpression of phosphorylated 4E-BP1 predicts for tumor recurrence and reduced survival in cervical carcinoma treated with postoperative radiotherapy. International journal of radiation oncology, biology, physics 23 19362787
2006 Clofibrate treatment promotes branched-chain amino acid catabolism and decreases the phosphorylation state of mTOR, eIF4E-BP1, and S6K1 in rat liver. Life sciences 23 16616211
2004 Characterizing the interaction of the mammalian eIF4E-related protein 4EHP with 4E-BP1. FEBS letters 23 15094042
2003 Ser-64 and Ser-111 in PHAS-I are dispensable for insulin-stimulated dissociation from eIF4E. The Journal of biological chemistry 23 14507920
2012 Translational homeostasis via eIF4E and 4E-BP1. Molecular cell 22 22749396
2018 Ferulic acid ameliorates cerebral infarction by activating Akt/mTOR/4E‑BP1/Bcl‑2 anti‑apoptotic signaling in the penumbral cortex following permanent cerebral ischemia in rats. Molecular medicine reports 21 30569126
2011 Sensitivity of global translation to mTOR inhibition in REN cells depends on the equilibrium between eIF4E and 4E-BP1. PloS one 21 22216185
2010 Resistance to discodermolide, a microtubule-stabilizing agent and senescence inducer, is 4E-BP1-dependent. Proceedings of the National Academy of Sciences of the United States of America 21 21173253
1999 Striking multiplicity of eIF4E-BP1 phosphorylated isoforms identified by 2D gel electrophoresis regulation by heat shock. European journal of biochemistry 21 10504405