Eif4ebp1

Summary

Gene Symbol: Eif4ebp1
Description: eukaryotic translation initiation factor 4E binding protein 1
Alias: 4e-bp1, AA959816, PHAS-I, eukaryotic translation initiation factor 4E-binding protein 1, eIF4E-binding protein 1, phosphorylated heat- and acid-stable protein regulated by insulin 1
Species: mouse
Products:     Eif4ebp1

Top Publications

  1. Romasko E, Amarnath D, Midic U, Latham K. Association of maternal mRNA and phosphorylated EIF4EBP1 variants with the spindle in mouse oocytes: localized translational control supporting female meiosis in mammals. Genetics. 2013;195:349-58 pubmed publisher
    ..We also find that the key translational regulator, EIF4EBP1, undergoes a dynamic and complex spatially regulated pattern of phosphorylation at sites that regulate its ..
  2. Zhang D, Contu R, Latronico M, Zhang J, Zhang J, Rizzi R, et al. MTORC1 regulates cardiac function and myocyte survival through 4E-BP1 inhibition in mice. J Clin Invest. 2010;120:2805-16 pubmed publisher
    ..Because the effects of reduced MTOR activity were mediated through increased 4E-BP1 inhibitory activity, blunting this mechanism may represent a novel therapeutic strategy for improving cardiac function in clinical HF. ..
  3. Tsukiyama Kohara K, Poulin F, Kohara M, DeMaria C, Cheng A, Wu Z, et al. Adipose tissue reduction in mice lacking the translational inhibitor 4E-BP1. Nat Med. 2001;7:1128-32 pubmed
    ..We investigated the biological function of 4E-BP1 by disrupting its gene (Eif4ebp1) in the mouse...
  4. Hentges K, Sirry B, Gingeras A, Sarbassov D, Sonenberg N, Sabatini D, et al. FRAP/mTOR is required for proliferation and patterning during embryonic development in the mouse. Proc Natl Acad Sci U S A. 2001;98:13796-801 pubmed
    ..Our studies also determined that rapamycin treatment of the early embryo results in a phenotype indistinguishable from the FRAP mutant, demonstrating that rapamycin has teratogenic activity. ..
  5. 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 ..
  6. Distefano G, Boca M, Rowe I, Wodarczyk C, Ma L, Piontek K, et al. Polycystin-1 regulates extracellular signal-regulated kinase-dependent phosphorylation of tuberin to control cell size through mTOR and its downstream effectors S6K and 4EBP1. Mol Cell Biol. 2009;29:2359-71 pubmed publisher
    ..We provide a detailed molecular mechanism by which PC-1 can inhibit the mTOR pathway and regulate cell size. ..
  7. Constantinou C, Clemens M. Regulation of translation factors eIF4GI and 4E-BP1 during recovery of protein synthesis from inhibition by p53. Cell Death Differ. 2007;14:576-85 pubmed
  8. 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. ..
  9. 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. ..

More Information

Publications84

  1. Dennis M, Schrufer T, Bronson S, Kimball S, Jefferson L. Hyperglycemia-induced O-GlcNAcylation and truncation of 4E-BP1 protein in liver of a mouse model of type 1 diabetes. J Biol Chem. 2011;286:34286-97 pubmed publisher
    ..These findings provide insight into the pathogenesis of metabolic abnormalities associated with diabetes. ..
  2. 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. ..
  3. 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
  4. 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. ..
  5. Kuang X, Shen J, Wong P, Yan M. Deregulation of mTOR signaling is involved in thymic lymphoma development in Atm-/- mice. Biochem Biophys Res Commun. 2009;383:368-72 pubmed publisher
    ..These results indicate that mTOR downstream effector 4EBP1 is essential for normal thymocyte proliferation, but deregulation of 4EBP1 in Atm deficiency is a major factor driving thymic lymphomagenesis in the animals. ..
  6. 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. ..
  7. Vijayaraj P, Kröger C, Reuter U, Windoffer R, Leube R, Magin T. Keratins regulate protein biosynthesis through localization of GLUT1 and -3 upstream of AMP kinase and Raptor. J Cell Biol. 2009;187:175-84 pubmed publisher
    ..Our findings demonstrate a novel keratin function upstream of mTOR signaling via GLUT localization and have implications for pathomechanisms and therapy approaches for keratin disorders and the analysis of other gene families. ..
  8. Feldman M, Apsel B, Uotila A, Loewith R, Knight Z, Ruggero D, et al. Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. PLoS Biol. 2009;7:e38 pubmed publisher
    ..These potent new pharmacological agents complement rapamycin in the study of mTOR and its role in normal physiology and human disease. ..
  9. Goo C, Lim H, Ho Q, Too H, Clement M, Wong K. PTEN/Akt signaling controls mitochondrial respiratory capacity through 4E-BP1. PLoS ONE. 2012;7:e45806 pubmed publisher
    ..In conclusion, PTEN inactivation bestowed a bioenergetic advantage to the cells by up-regulating mitochondrial respiratory capacity through the 4E-BP1-mediated protein translation pathway. ..
  10. Shives K, Massey A, May N, Morrison T, Beckham J. 4EBP-Dependent Signaling Supports West Nile Virus Growth and Protein Expression. Viruses. 2016;8: pubmed
    ..Our data suggest that the mTORC1/4EBP/eIF4E signaling axis is activated to support the translation of the WNV genome. ..
  11. Marabita M, Baraldo M, Solagna F, Ceelen J, Sartori R, Nolte H, et al. S6K1 Is Required for Increasing Skeletal Muscle Force during Hypertrophy. Cell Rep. 2016;17:501-513 pubmed publisher
    ..These findings identify S6K1 as a crucial player for maintaining muscle function during hypertrophy. ..
  12. Yang L, Miao L, Liang F, Huang H, Teng X, Li S, et al. The mTORC1 effectors S6K1 and 4E-BP play different roles in CNS axon regeneration. Nat Commun. 2014;5:5416 pubmed publisher
    ..Both activation and inhibition of S6K1 decrease the effect of PTEN deletion on axon regeneration, implicating a dual role of S6K1 in regulating axon growth. ..
  13. Sans M, DiMagno M, D Alecy L, Williams J. Caerulein-induced acute pancreatitis inhibits protein synthesis through effects on eIF2B and eIF4F. Am J Physiol Gastrointest Liver Physiol. 2003;285:G517-28 pubmed
  14. Elia A, Constantinou C, Clemens M. Effects of protein phosphorylation on ubiquitination and stability of the translational inhibitor protein 4E-BP1. Oncogene. 2008;27:811-22 pubmed
    ..We suggest that the phosphorylation of 4E-BP1 may play a dual role in the regulation of protein synthesis, both reducing the affinity of 4E-BP1 for eIF4E and promoting the conversion of 4E-BP1 to alternative, polyubiquitinated forms. ..
  15. Lynch M, Fitzgerald C, Johnston K, Wang S, Schmidt E. Activated eIF4E-binding protein slows G1 progression and blocks transformation by c-myc without inhibiting cell growth. J Biol Chem. 2004;279:3327-39 pubmed
    ..It further identifies G(1) control by translation initiation factors as an essential genetic target of c-myc that is necessary for its ability to transform cells. ..
  16. 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. ..
  17. 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. ..
  18. 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. ..
  19. Lan B, Wan Y, Pan S, Wang Y, Yang Y, Leng Q, et al. Parthenolide induces autophagy via the depletion of 4E-BP1. Biochem Biophys Res Commun. 2015;456:434-9 pubmed publisher
    ..Surprisingly, PTL decreased the level of translation initiation factor eIF4E binding protein 1 (4E-BP1) in correlation with autophagy...
  20. Wang B, Ducker G, Barczak A, Barbeau R, Erle D, Shokat K. The mammalian target of rapamycin regulates cholesterol biosynthetic gene expression and exhibits a rapamycin-resistant transcriptional profile. Proc Natl Acad Sci U S A. 2011;108:15201-6 pubmed publisher
    ..PP242 caused 1,666 genes to be differentially expressed whereas rapamycin affected only 88 genes. Our analysis provides a genomewide view of the transcriptional outputs of mTOR signaling that are insensitive to rapamycin. ..
  21. Landau G, Bercovich Z, Park M, Kahana C. The role of polyamines in supporting growth of mammalian cells is mediated through their requirement for translation initiation and elongation. J Biol Chem. 2010;285:12474-81 pubmed publisher
    ..Finally, we show that either polyamine depletion or GC7 treatment induced eIF2alpha phosphorylation and reduced phosphorylation of 4E-BP, thus setting the molecular basis for the observed inhibition of translation initiation. ..
  22. Dodd K, Yang J, Shen M, Sampson J, Tee A. mTORC1 drives HIF-1? and VEGF-A signalling via multiple mechanisms involving 4E-BP1, S6K1 and STAT3. Oncogene. 2015;34:2239-50 pubmed publisher
    ..Our work has important implications for the treatment of vascularised tumours, where mTORC1 acts as a central mediator of STAT3, HIF-1?, VEGF-A and angiogenesis via multiple signalling mechanisms. ..
  23. Lai L, Lilley B, Sanes J, McMahon A. Lkb1/Stk11 regulation of mTOR signaling controls the transition of chondrocyte fates and suppresses skeletal tumor formation. Proc Natl Acad Sci U S A. 2013;110:19450-5 pubmed publisher
    ..These findings highlight a critical requirement for integration of mammalian target of rapamycin activity into developmental decision-making during mammalian skeletogenesis. ..
  24. Gan B, Peng X, Nagy T, Alcaraz A, Gu H, Guan J. Role of FIP200 in cardiac and liver development and its regulation of TNFalpha and TSC-mTOR signaling pathways. J Cell Biol. 2006;175:121-33 pubmed
    ..Together, our results reveal that FIP200 functions as a regulatory node to couple two important signaling pathways to regulate cell growth and survival during mouse embryogenesis. ..
  25. Rong L, Livingstone M, Sukarieh R, Petroulakis E, Gingras A, Crosby K, et al. Control of eIF4E cellular localization by eIF4E-binding proteins, 4E-BPs. RNA. 2008;14:1318-27 pubmed publisher
    ..A dramatic loss of nuclear 4E-BP1 occurs in c-Ha-Ras-expressing MEFs, which fail to show starvation-induced nuclear accumulation of eIF4E. Therefore, 4E-BP1 is a regulator of eIF4E cellular localization. ..
  26. Dumstorf C, Konicek B, McNulty A, Parsons S, Furic L, Sonenberg N, et al. Modulation of 4E-BP1 function as a critical determinant of enzastaurin-induced apoptosis. Mol Cancer Ther. 2010;9:3158-63 pubmed publisher
    ..These data highlight the importance of modulating 4E-BP1 function, and eIF4F complex levels, in the direct antitumor effect of enzastaurin and suggest that 4E-BP1 function may serve as a promising determinant of enzastaurin activity. ..
  27. Kassai H, Sugaya Y, Noda S, Nakao K, Maeda T, Kano M, et al. Selective activation of mTORC1 signaling recapitulates microcephaly, tuberous sclerosis, and neurodegenerative diseases. Cell Rep. 2014;7:1626-1639 pubmed publisher
    ..Our findings demonstrate that mTORC1 plays different roles in developmental and adult stages and contributes to human neurological diseases. ..
  28. Wang C, Cigliano A, Jiang L, Li X, Fan B, Pilo M, et al. 4EBP1/eIF4E and p70S6K/RPS6 axes play critical and distinct roles in hepatocarcinogenesis driven by AKT and N-Ras proto-oncogenes in mice. Hepatology. 2015;61:200-13 pubmed publisher
    ..The mTORC1 effectors, RPS6 and eIF4E, play distinct roles and are both necessary for AKT/Ras hepatocarcinogenesis. These new findings might open the way for innovative therapies against human HCC. ..
  29. Choo A, Yoon S, Kim S, Roux P, Blenis J. Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation. Proc Natl Acad Sci U S A. 2008;105:17414-9 pubmed publisher
    ..Finally, we show that mTOR catalytic inhibitors are effective inhibitors of the rapamycin-resistant phenotype. ..
  30. 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. ..
  31. Yamaguchi S, Ishihara H, Yamada T, Tamura A, Usui M, Tominaga R, et al. ATF4-mediated induction of 4E-BP1 contributes to pancreatic beta cell survival under endoplasmic reticulum stress. Cell Metab. 2008;7:269-76 pubmed publisher
    ..4E-BP1 expression was increased in islets under ER stress in several mouse models of diabetes. The Eif4ebp1 gene encoding 4E-BP1 was revealed to be a direct target of the transcription factor ATF4...
  32. Kannan Thulasiraman P, Dolniak B, Kaur S, Sassano A, Kalvakolanu D, Hay N, et al. Role of the translational repressor 4E-BP1 in the regulation of p21(Waf1/Cip1) expression by retinoids. Biochem Biophys Res Commun. 2008;368:983-9 pubmed publisher
    ..Altogether, these findings strongly suggest a key regulatory role for the translational repressor 4E-BP1 in the generation of retinoid-dependent functional responses. ..
  33. Figlia G, Norrmen C, Pereira J, Gerber D, Suter U. Dual function of the PI3K-Akt-mTORC1 axis in myelination of the peripheral nervous system. elife. 2017;6: pubmed publisher
    ..An ensuing decline in mTORC1 activity is crucial to allow myelination to start, while remaining mTORC1 activity drives myelin growth. ..
  34. Conn C, Qian S. Nutrient signaling in protein homeostasis: an increase in quantity at the expense of quality. Sci Signal. 2013;6:ra24 pubmed publisher
    ..Our results reveal a mechanistic connection between mTORC1 and protein quality, highlighting the central role of nutrient signaling in growth and aging. ..
  35. 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. ..
  36. 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
  37. 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
  38. Darido C, Georgy S, Wilanowski T, Dworkin S, Auden A, Zhao Q, et al. Targeting of the tumor suppressor GRHL3 by a miR-21-dependent proto-oncogenic network results in PTEN loss and tumorigenesis. Cancer Cell. 2011;20:635-48 pubmed publisher
    ..Our data define the GRHL3-PTEN axis as a critical tumor suppressor pathway in SCC. ..
  39. 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. ..
  40. Blackshear P, Stumpo D, Carballo E, Lawrence J. Disruption of the gene encoding the mitogen-regulated translational modulator PHAS-I in mice. J Biol Chem. 1997;272:31510-4 pubmed
  41. Avet Rochex A, Carvajal N, Christoforou C, Yeung K, Maierbrugger K, Hobbs C, et al. Unkempt is negatively regulated by mTOR and uncouples neuronal differentiation from growth control. PLoS Genet. 2014;10:e1004624 pubmed publisher
    ..Finally, we show that Unkempt-like is expressed in the developing mouse retina and in neural stem/progenitor cells, suggesting that the role of Unk in neurogenesis may be conserved in mammals. ..
  42. Villalonga P, Fernandez De Mattos S, Ridley A. RhoE inhibits 4E-BP1 phosphorylation and eIF4E function impairing cap-dependent translation. J Biol Chem. 2009;284:35287-96 pubmed publisher
  43. Ma A, Wang L, Gao Y, Chang Z, Peng H, Zeng N, et al. Tsc1 deficiency-mediated mTOR hyperactivation in vascular endothelial cells causes angiogenesis defects and embryonic lethality. Hum Mol Genet. 2014;23:693-705 pubmed publisher
    ..We postulated that disruption of normal angiogenic pathways through hyperactive mTOR signaling maybe the mechanism that lead to deranged vascular pathogenesis in the tuberous sclerosis complex. ..
  44. Cao R, Robinson B, Xu H, Gkogkas C, Khoutorsky A, Alain T, et al. Translational control of entrainment and synchrony of the suprachiasmatic circadian clock by mTOR/4E-BP1 signaling. Neuron. 2013;79:712-24 pubmed publisher
    ..Knockout (KO) of Eif4ebp1 (gene encoding 4E-BP1) leads to upregulation of VIP and higher amplitude of molecular rhythms in the SCN...
  45. Guntur K, Guilherme A, Xue L, Chawla A, Czech M. Map4k4 negatively regulates peroxisome proliferator-activated receptor (PPAR) gamma protein translation by suppressing the mammalian target of rapamycin (mTOR) signaling pathway in cultured adipocytes. J Biol Chem. 2010;285:6595-603 pubmed publisher
    ..These data show that Map4k4 negatively regulates PPARgamma post-transcriptionally, by attenuating mTOR signaling and a 4E-BP1-dependent mechanism. ..
  46. 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. ..
  47. Lekmine F, Uddin S, Sassano A, Parmar S, Brachmann S, Majchrzak B, et al. Activation of the p70 S6 kinase and phosphorylation of the 4E-BP1 repressor of mRNA translation by type I interferons. J Biol Chem. 2003;278:27772-80 pubmed
    ..Altogether, our data establish that the Type I IFN receptor-activated PI 3'-kinase pathway mediates activation of the p70 S6 kinase and inactivation of 4E-BP1, to regulate mRNA translation and induction of Type I IFN responses. ..
  48. Sayano T, Kawakami Y, Kusada W, Suzuki T, Kawano Y, Watanabe A, et al. L-serine deficiency caused by genetic Phgdh deletion leads to robust induction of 4E-BP1 and subsequent repression of translation initiation in the developing central nervous system. FEBS J. 2013;280:1502-17 pubmed publisher
    ..Here we demonstrate that mRNA of Eif4ebp1 encoding eukaryotic initiation factor 4 binding protein 1 and its protein, 4E-BP1, are markedly induced in the ..
  49. Tsai S, Rodriguez A, Dastidar S, Del Greco E, Carr K, Sitzmann J, et al. Increased 4E-BP1 Expression Protects against Diet-Induced Obesity and Insulin Resistance in Male Mice. Cell Rep. 2016;16:1903-14 pubmed publisher
    ..Here, we link these differences to expression of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), which, upon HFD feeding, becomes significantly reduced in the skeletal ..
  50. Tărlungeanu D, Deliu E, Dotter C, Kara M, Janiesch P, Scalise M, et al. Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder. Cell. 2016;167:1481-1494.e18 pubmed publisher
    ..Our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for the BCAA in human brain function. ..
  51. Azar R, Alard A, Susini C, Bousquet C, Pyronnet S. 4E-BP1 is a target of Smad4 essential for TGFbeta-mediated inhibition of cell proliferation. EMBO J. 2009;28:3514-22 pubmed publisher
    ..Thus, 4E-BP1 gene appears critical for TGFbeta/Smad4-mediated inhibition of cell proliferation. ..
  52. 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. ..
  53. 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. ..
  54. Constantinou C, Clemens M. Regulation of the phosphorylation and integrity of protein synthesis initiation factor eIF4GI and the translational repressor 4E-BP1 by p53. Oncogene. 2005;24:4839-50 pubmed
    ..These data suggest that the inhibition of protein synthesis by p53 is largely independent of the regulation of rapamycin-sensitive mTOR in the system under investigation. ..
  55. Goodfellow I, Chaudhry Y, Gioldasi I, Gerondopoulos A, Natoni A, Labrie L, et al. Calicivirus translation initiation requires an interaction between VPg and eIF 4 E. EMBO Rep. 2005;6:968-72 pubmed
    ..This work lends support to the idea that calicivirus VPg acts as a novel 'cap substitute' during initiation of translation on virus mRNA. ..
  56. 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. ..
  57. 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. ..
  58. Otulakowski G, Duan W, Gandhi S, O Brodovich H. Steroid and oxygen effects on eIF4F complex, mTOR, and ENaC translation in fetal lung epithelia. Am J Respir Cell Mol Biol. 2007;37:457-66 pubmed
    ..We speculate that at birth increased Po(2) acts with GC through an mTOR-related pathway to increase alpha-ENaC protein synthesis, thereby promoting lung fluid absorption. ..
  59. Lawrence J, Abraham R. PHAS/4E-BPs as regulators of mRNA translation and cell proliferation. Trends Biochem Sci. 1997;22:345-9 pubmed
    ..PHAS/4E-BPs, a recently discovered family of elF4E-binding, proteins, appear to play a key role in this process, as well as in the control of cell proliferation. ..
  60. Shin J, Méndez López I, Hong M, Wang Y, Tanji K, Wu W, et al. Lamina-associated polypeptide 1 is dispensable for embryonic myogenesis but required for postnatal skeletal muscle growth. Hum Mol Genet. 2017;26:65-78 pubmed publisher
    ..Our results demonstrate that early embryonic depletion of LAP1 does not impair myogenesis but that it is necessary for postnatal skeletal muscle growth. ..
  61. Wang L, Zhang Y, Wang X, Song Z, Wang W. [Expression and significance of mTOR/4EBP1/HIF-1?/VEGF signaling pathway in lung tissues of asthmatic mice]. Zhongguo Dang Dai Er Ke Za Zhi. 2017;19:104-110 pubmed
    ..p-mTOR, p-4EBP1, HIF-1? and VEGF together are involved in the pathogenesis of asthma. Rapamycin treatment can block this signaling pathway, suggesting that this pathway can be used as a novel target for asthma treatment. ..
  62. Ohgaki R, Ohmori T, Hara S, Nakagomi S, Kanai Azuma M, Kaneda Nakashima K, et al. Essential Roles of L-Type Amino Acid Transporter 1 in Syncytiotrophoblast Development by Presenting Fusogenic 4F2hc. Mol Cell Biol. 2017;37: pubmed publisher
  63. Lin T, Kong X, Saltiel A, Blackshear P, Lawrence J. Control of PHAS-I by insulin in 3T3-L1 adipocytes. Synthesis, degradation, and phosphorylation by a rapamycin-sensitive and mitogen-activated protein kinase-independent pathway. J Biol Chem. 1995;270:18531-8 pubmed
    ..Rapamycin may inhibit translation initiation by increasing PHAS-I binding to eIF-4E. ..
  64. 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
  65. Tsuchihashi N, Hayashi K, Dan K, Goto F, Nomura Y, Fujioka M, et al. Autophagy through 4EBP1 and AMPK regulates oxidative stress-induced premature senescence in auditory cells. Oncotarget. 2015;6:3644-55 pubmed
    ..Our results also indicate that AMPK may regulate premature senescence in auditory cells in an autophagy-dependent and independent manner. ..
  66. Stephenson A, Seidel E. Analysis of the interactions of Nrf-2, PMF-1, and CSN-7 with the 5'-flanking sequence of the mouse 4E-BP1 gene. Life Sci. 2006;79:1221-7 pubmed
    ..Since polyamines increase expression of the 4E-BP1 gene, it seems likely that formation of this complex is involved in its transcriptional regulation...
  67. Pétremand J, Bulat N, Butty A, Poussin C, Rütti S, Au K, et al. Involvement of 4E-BP1 in the protection induced by HDLs on pancreatic beta-cells. Mol Endocrinol. 2009;23:1572-86 pubmed publisher
    ..Our results indicate that HDLs can protect beta-cells through modulation of 4E-BP1 depending on the type of stress stimuli. ..
  68. 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. ..
  69. 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. ..
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