Gene Symbol: Eif4ebp2
Description: eukaryotic translation initiation factor 4E binding protein 2
Alias: 2810011I19Rik, 4E-BP2, AA792569, BC010348, PHAS-II, eukaryotic translation initiation factor 4E-binding protein 2, eIF4E-binding protein 2, phosphorylated heat- and acid-stable protein regulated by insulin 2
Species: mouse
Products:     Eif4ebp2

Top Publications

  1. Coleman L, Peter M, Teall T, Brannan R, Hanby A, Honarpisheh H, et al. Combined analysis of eIF4E and 4E-binding protein expression predicts breast cancer survival and estimates eIF4E activity. Br J Cancer. 2009;100:1393-9 pubmed publisher
    ..We conclude that eIF4E's influence on cancer survival is modulated substantially by 4E-BPs, and that combined pathway analyses can estimate functional eIF4E. ..
  2. Pause A, Belsham G, Gingras A, Donze O, Lin T, Lawrence J, et al. Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function. Nature. 1994;371:762-7 pubmed
    ..The action of this new regulator of protein synthesis is therefore modulated by insulin, which acts to stimulate the overall rate of translation and promote cell growth. ..
  3. Le Bacquer O, Petroulakis E, Paglialunga S, Poulin F, Richard D, Cianflone K, et al. Elevated sensitivity to diet-induced obesity and insulin resistance in mice lacking 4E-BP1 and 4E-BP2. J Clin Invest. 2007;117:387-96 pubmed
    ..These data clearly demonstrate the role of 4E-BPs as a metabolic brake in the development of obesity and reinforce the idea that deregulated mTOR signaling is associated with the development of the metabolic syndrome. ..
  4. Bidinosti M, Ran I, Sanchez Carbente M, Martineau Y, Gingras A, Gkogkas C, et al. Postnatal deamidation of 4E-BP2 in brain enhances its association with raptor and alters kinetics of excitatory synaptic transmission. Mol Cell. 2010;37:797-808 pubmed publisher
    ..4E-BP2 deamidation may represent a compensatory mechanism for the developmental reduction of PI3K-Akt-mTOR signaling. ..
  5. Kim Y, von Weymarn L, Larsson O, Fan D, UNDERWOOD J, Peterson M, et al. Eukaryotic initiation factor 4E binding protein family of proteins: sentinels at a translational control checkpoint in lung tumor defense. Cancer Res. 2009;69:8455-62 pubmed publisher
    ..Our study provides in vivo proof for a translational control checkpoint in lung tumor defense. ..
  6. Dennis M, Jefferson L, Kimball S. Role of p70S6K1-mediated phosphorylation of eIF4B and PDCD4 proteins in the regulation of protein synthesis. J Biol Chem. 2012;287:42890-9 pubmed publisher
  7. Banko J, Poulin F, Hou L, DeMaria C, Sonenberg N, Klann E. The translation repressor 4E-BP2 is critical for eIF4F complex formation, synaptic plasticity, and memory in the hippocampus. J Neurosci. 2005;25:9581-90 pubmed
    ..These results suggest a crucial role for proper regulation of the eIF4F complex by 4E-BP2 during LTP and learning and memory in the mouse hippocampus. ..
  8. Schrufer T, Antonetti D, Sonenberg N, Kimball S, Gardner T, Jefferson L. Ablation of 4E-BP1/2 prevents hyperglycemia-mediated induction of VEGF expression in the rodent retina and in Muller cells in culture. Diabetes. 2010;59:2107-16 pubmed publisher
    ..These findings provide new insights into potential targets for treatment of diabetic retinopathy. ..
  9. Dowling R, Topisirovic I, Alain T, Bidinosti M, Fonseca B, Petroulakis E, et al. mTORC1-mediated cell proliferation, but not cell growth, controlled by the 4E-BPs. Science. 2010;328:1172-6 pubmed publisher
    ..Thus, control of cell size and cell cycle progression appear to be independent in mammalian cells, whereas in lower eukaryotes, 4E-BPs influence both cell growth and proliferation. ..

More Information


  1. Banko J, Merhav M, Stern E, Sonenberg N, Rosenblum K, Klann E. Behavioral alterations in mice lacking the translation repressor 4E-BP2. Neurobiol Learn Mem. 2007;87:248-56 pubmed
  2. Colina R, Costa Mattioli M, Dowling R, Jaramillo M, Tai L, Breitbach C, et al. Translational control of the innate immune response through IRF-7. Nature. 2008;452:323-8 pubmed publisher
    ..Furthermore, mice with both 4E- and 4E-BP2 genes (also known as Eif4ebp1 and Eif4ebp2, respectively) knocked out are resistant to vesicular stomatitis virus infection, and this correlates with an ..
  3. Lin T, Lawrence J. Control of the translational regulators PHAS-I and PHAS-II by insulin and cAMP in 3T3-L1 adipocytes. J Biol Chem. 1996;271:30199-204 pubmed
    ..In summary, our results indicate that PHAS-I and -II are controlled by the mammalian target of rapamycin and p70(S6K) signaling pathway and that in 3T3-L1 adipocytes this pathway is inhibited by increased cAMP. ..
  4. Shen C, Houghton P. The mTOR pathway negatively controls ATM by up-regulating miRNAs. Proc Natl Acad Sci U S A. 2013;110:11869-74 pubmed publisher
    ..Our findings have identified a negative feedback loop for the signaling between ATM and mTOR pathways and suggest that oncogenic growth signals may promote tumorigenesis by dampening the ATM checkpoint. ..
  5. Dennis M, Shenberger J, Stanley B, Kimball S, Jefferson L. Hyperglycemia mediates a shift from cap-dependent to cap-independent translation via a 4E-BP1-dependent mechanism. Diabetes. 2013;62:2204-14 pubmed publisher
    ..Taken together, these data provide evidence for a novel mechanism whereby O-GlcNAcylation of 4E-BP1 mediates translational control of hepatic gene expression. ..
  6. Petroulakis E, Parsyan A, Dowling R, LeBacquer O, Martineau Y, Bidinosti M, et al. p53-dependent translational control of senescence and transformation via 4E-BPs. Cancer Cell. 2009;16:439-46 pubmed publisher
    ..Our data demonstrate a role for 4E-BPs in senescence and tumorigenesis and highlight a p53-mediated mechanism of senescence through a 4E-BP-dependent pathway. ..
  7. Miller W, Mihailescu M, Yang C, Barber A, Kimball S, Jefferson L, et al. The Translational Repressor 4E-BP1 Contributes to Diabetes-Induced Visual Dysfunction. Invest Ophthalmol Vis Sci. 2016;57:1327-37 pubmed publisher
    ..The findings support a model whereby elevated 4E-BP1 expression observed in the retina of diabetic rodents is the result of O-GlcNAcylation of 4E-BP1 within its PEST motif. ..
  8. Carnevalli L, Masuda K, Frigerio F, Le Bacquer O, Um S, Gandin V, et al. S6K1 plays a critical role in early adipocyte differentiation. Dev Cell. 2010;18:763-74 pubmed publisher
    ..These results led to the conclusion that a lack of S6K1 impairs the generation of de novo adipocytes when mice are challenged with a HFD, consistent with a reduction in early adipocyte progenitors. ..
  9. Yu X, Pandey S, Booten S, Murray S, Monia B, Bhanot S. Reduced adiposity and improved insulin sensitivity in obese mice with antisense suppression of 4E-BP2 expression. Am J Physiol Endocrinol Metab. 2008;294:E530-9 pubmed publisher
    ..These data demonstrate for the first time that peripheral 4E-BP2 plays an important role in metabolism and energy homeostasis. ..
  10. Dennis M, Kimball S, Jefferson L. Mechanistic target of rapamycin complex 1 (mTORC1)-mediated phosphorylation is governed by competition between substrates for interaction with raptor. J Biol Chem. 2013;288:10-9 pubmed publisher
    ..Together, these findings support the conclusion that, in the absence of 4E-BP proteins, mTORC1-mediated phosphorylation of p70S6K1 is elevated by a reduction in competition between the two substrates for interaction with raptor. ..
  11. Gkogkas C, Khoutorsky A, Ran I, Rampakakis E, Nevarko T, Weatherill D, et al. Autism-related deficits via dysregulated eIF4E-dependent translational control. Nature. 2013;493:371-7 pubmed publisher
    ..Mice that have the gene encoding 4E-BP2 (Eif4ebp2) knocked out exhibit an increased ratio of excitatory to inhibitory synaptic inputs and autistic-like behaviours (..
  12. Sukarieh R, Sonenberg N, Pelletier J. The eIF4E-binding proteins are modifiers of cytoplasmic eIF4E relocalization during the heat shock response. Am J Physiol Cell Physiol. 2009;296:C1207-17 pubmed publisher
    ..Herein, we demonstrate that localization of eIF4E to SGs is dependent on the presence of a family of repressor proteins, eIF4E-binding proteins (4E-BPs). Our results demonstrate that 4E-BPs regulate the SG localization of eIF4E. ..
  13. Signer R, Qi L, Zhao Z, Thompson D, Sigova A, Fan Z, et al. The rate of protein synthesis in hematopoietic stem cells is limited partly by 4E-BPs. Genes Dev. 2016;30:1698-703 pubmed publisher
  14. Tsukiyama Kohara K, Vidal S, Gingras A, Glover T, Hanash S, Heng H, et al. Tissue distribution, genomic structure, and chromosome mapping of mouse and human eukaryotic initiation factor 4E-binding proteins 1 and 2. Genomics. 1996;38:353-63 pubmed
    ..Mouse 4E-BP1 and 4E-BP2 map to chromosomes 8 (A4-B1) and 10 (B4-B5), respectively, and human 4E-BP1 and 4E-BP2 localize to chromosomes 8p12 and 10q21-q22, respectively. ..
  15. Zhou J, Saba J. Identification of the first mammalian sphingosine phosphate lyase gene and its functional expression in yeast. Biochem Biophys Res Commun. 1998;242:502-7 pubmed
    ..Chromosomal localization mapped this SPL gene to Chromosome 10 at 32 cM. Here, we report the identification of the first mammalian sphingosine phosphate lyase gene. ..
  16. Bidinosti M, Martineau Y, Frank F, Sonenberg N. Repair of isoaspartate formation modulates the interaction of deamidated 4E-BP2 with mTORC1 in brain. J Biol Chem. 2010;285:19402-8 pubmed publisher
    ..Further, we show that 4E-BP2 containing isoaspartates lacks the augmented association with raptor that is a feature of deamidated 4E-BP2. ..
  17. Santini E, Huynh T, Macaskill A, Carter A, Pierre P, Ruggero D, et al. Exaggerated translation causes synaptic and behavioural aberrations associated with autism. Nature. 2013;493:411-5 pubmed publisher
    ..Our findings demonstrate a causal relationship between exaggerated cap-dependent translation, synaptic dysfunction and aberrant behaviours associated with autism. ..
  18. Blandino Rosano M, Scheys J, Jimenez Palomares M, Barbaresso R, Bender A, Yanagiya A, et al. 4E-BP2/SH2B1/IRS2 Are Part of a Novel Feedback Loop That Controls ?-Cell Mass. Diabetes. 2016;65:2235-48 pubmed publisher
    ..Our data identify SH2B1 as a major regulator of IRS2 stability, demonstrate a novel feedback mechanism linking mTORC1 signaling with IRS2, and identify 4E-BP2 as a major regulator of proliferation and survival of ?-cells. ..
  19. Truitt M, Conn C, Shi Z, Pang X, Tokuyasu T, Coady A, et al. Differential Requirements for eIF4E Dose in Normal Development and Cancer. Cell. 2015;162:59-71 pubmed publisher
    ..Our findings indicate eIF4E is maintained at levels in excess for normal development that are hijacked by cancer cells to drive a translational program supporting tumorigenesis. ..
  20. Chung J, Bauer D, Ghamari A, Nizzi C, Deck K, Kingsley P, et al. The mTORC1/4E-BP pathway coordinates hemoglobin production with L-leucine availability. Sci Signal. 2015;8:ra34 pubmed publisher
  21. Singh M, Shin Y, Yang X, Zehr B, Chakrabarti P, Kandror K. 4E-BPs Control Fat Storage by Regulating the Expression of Egr1 and ATGL. J Biol Chem. 2015;290:17331-8 pubmed publisher
    ..In confirmation of this model, we show that 4E-BP1/2-null MEFs express less ATGL and accumulate more fat than control cells, while knock down of Egr1 in 4E-BP1/2-null MEFs increases ATGL expression and decreases fat storage. ..
  22. Lin T, Hsieh L, Kimura T, Malone T, Bordey A. Normalizing translation through 4E-BP prevents mTOR-driven cortical mislamination and ameliorates aberrant neuron integration. Proc Natl Acad Sci U S A. 2016;113:11330-11335 pubmed
    ..These data show that many aspects of abnormal brain cytoarchitecture can be prevented by manipulating a single intracellular process downstream of mTORC1, cap-dependent translation. ..
  23. Aguilar Valles A, Matta Camacho E, Khoutorsky A, Gkogkas C, Nader K, Lacaille J, et al. Inhibition of Group I Metabotropic Glutamate Receptors Reverses Autistic-Like Phenotypes Caused by Deficiency of the Translation Repressor eIF4E Binding Protein 2. J Neurosci. 2015;35:11125-32 pubmed publisher
    ..Deletion of the eukaryotic initiation factor 4E (eIF4E)-binding protein 2 gene (Eif4ebp2), encoding the suppressor of mRNA translation initiation 4E-BP2, leads to an imbalance in excitatory-to-..
  24. Biggs W, Cavenee W, Arden K. Identification and characterization of members of the FKHR (FOX O) subclass of winged-helix transcription factors in the mouse. Mamm Genome. 2001;12:416-25 pubmed
    ..Further characterization will provide insight into the roles of members of the FKHR subfamily of forkhead-related genes during both normal and neoplastic development. ..
  25. Gelinas J, Banko J, Hou L, Sonenberg N, Weeber E, Klann E, et al. ERK and mTOR signaling couple beta-adrenergic receptors to translation initiation machinery to gate induction of protein synthesis-dependent long-term potentiation. J Biol Chem. 2007;282:27527-35 pubmed
  26. Lebrun Julien F, Bachmann L, Norrmen C, Trötzmüller M, Köfeler H, Ruegg M, et al. Balanced mTORC1 activity in oligodendrocytes is required for accurate CNS myelination. J Neurosci. 2014;34:8432-48 pubmed publisher
    ..Our data demonstrate that a delicately balanced regulation of mTORC1 activation and action in oligodendrocytes is essential for CNS myelination, which has practical overtones for understanding CNS myelin disorders. ..
  27. Steiner J, Pruznak A, Deiter G, Navaratnarajah M, Kutzler L, Kimball S, et al. Disruption of genes encoding eIF4E binding proteins-1 and -2 does not alter basal or sepsis-induced changes in skeletal muscle protein synthesis in male or female mice. PLoS ONE. 2014;9:e99582 pubmed publisher
  28. Morita M, Gravel S, Chénard V, Sikström K, Zheng L, Alain T, et al. mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translational regulation. Cell Metab. 2013;18:698-711 pubmed publisher
  29. Bjur E, Larsson O, Yurchenko E, Zheng L, Gandin V, Topisirovic I, et al. Distinct translational control in CD4+ T cell subsets. PLoS Genet. 2013;9:e1003494 pubmed publisher
    ..Unexpectedly, eIF4E also affects Foxp3 expression and thereby lineage identity. Thus, mRNA-specific translational control directs both common and distinct cellular processes in CD4(+) T cell subsets. ..
  30. Khoutorsky A, Bonin R, Sorge R, Gkogkas C, Pawlowski S, Jafarnejad S, et al. Translational control of nociception via 4E-binding protein 1. elife. 2015;4: pubmed publisher
    ..Thus, translational control by 4E-BP1 downstream of mTOR effects the expression of neuroligin 1 and excitatory synaptic transmission in the spinal cord, and thereby contributes to enhanced mechanical nociception. ..
  31. Olson K, Booth G, Poulin F, Sonenberg N, Beretta L. Impaired myelopoiesis in mice lacking the repressors of translation initiation, 4E-BP1 and 4E-BP2. Immunology. 2009;128:e376-84 pubmed publisher
    ..These results represent the first in vivo evidence of the involvement of translation in the early phases of granulo-monocytic differentiation and further extend the role of translation in haematopoietic differentiation. ..
  32. Ran I, Gkogkas C, Vasuta C, Tartas M, Khoutorsky A, Laplante I, et al. Selective regulation of GluA subunit synthesis and AMPA receptor-mediated synaptic function and plasticity by the translation repressor 4E-BP2 in hippocampal pyramidal cells. J Neurosci. 2013;33:1872-86 pubmed publisher
    ..Thus, translational control through 4E-BP2 represents a unique mechanism for selective regulation of AMPAR synthesis, synaptic function, and long-term plasticity, important for hippocampal-dependent memory processes. ..
  33. Sinclair C, Bommakanti G, Gardinassi L, Loebbermann J, Johnson M, Hakimpour P, et al. mTOR regulates metabolic adaptation of APCs in the lung and controls the outcome of allergic inflammation. Science. 2017;357:1014-1021 pubmed publisher
    ..mTOR therefore mediates metabolic adaptation of APCs in distinct tissues, influencing the immunological character of allergic inflammation. ..