eIF4E

Summary

Gene Symbol: eIF4E
Description: eukaryotic translation initiation factor 4E
Alias: AUTS19, CBP, EIF4E1, EIF4EL1, EIF4F, eIF-4E, eukaryotic translation initiation factor 4E, eIF-4F 25 kDa subunit, eukaryotic translation initiation factor 4E-like 1, mRNA cap-binding protein
Species: human
Products:     eIF4E

Top Publications

  1. Lejbkowicz F, Goyer C, Darveau A, Neron S, Lemieux R, Sonenberg N. A fraction of the mRNA 5' cap-binding protein, eukaryotic initiation factor 4E, localizes to the nucleus. Proc Natl Acad Sci U S A. 1992;89:9612-6 pubmed
    ..These results suggest that eIF-4E is also involved in a nuclear function. ..
  2. 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
    Increased eukaryotic translation initiation factor 4E (eIF4E) expression occurs in many cancers, and makes fundamental contributions to carcinogenesis by stimulating the expression of cancer-related genes at post-transcriptional levels...
  3. Wang X, Yue P, Chan C, Ye K, Ueda T, Watanabe Fukunaga R, et al. Inhibition of mammalian target of rapamycin induces phosphatidylinositol 3-kinase-dependent and Mnk-mediated eukaryotic translation initiation factor 4E phosphorylation. Mol Cell Biol. 2007;27:7405-13 pubmed
    The initiation factor eukaryotic translation initiation factor 4E (eIF4E) plays a critical role in initiating translation of mRNAs, including those encoding oncogenic proteins...
  4. Ma X, Yoon S, Richardson C, Jülich K, Blenis J. SKAR links pre-mRNA splicing to mTOR/S6K1-mediated enhanced translation efficiency of spliced mRNAs. Cell. 2008;133:303-13 pubmed publisher
    ..Thus, SKAR-mediated recruitment of activated S6K1 to newly processed mRNPs serves as a conduit between mTOR checkpoint signaling and the pioneer round of translation when cells exist in conditions supportive of protein synthesis. ..
  5. Haghighat A, Mader S, Pause A, Sonenberg N. Repression of cap-dependent translation by 4E-binding protein 1: competition with p220 for binding to eukaryotic initiation factor-4E. EMBO J. 1995;14:5701-9 pubmed
    ..Thus, translational control by growth factors, insulin and mitogens is affected by changes in the relative affinities of 4E-BP1 and p220 for eIF-4E. ..
  6. Moerke N, Aktas H, Chen H, Cantel S, Reibarkh M, Fahmy A, et al. Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Cell. 2007;128:257-67 pubmed
    Assembly of the eIF4E/eIF4G complex has a central role in the regulation of gene expression at the level of translation initiation...
  7. Mader S, Lee H, Pause A, Sonenberg N. The translation initiation factor eIF-4E binds to a common motif shared by the translation factor eIF-4 gamma and the translational repressors 4E-binding proteins. Mol Cell Biol. 1995;15:4990-7 pubmed
    b>Eukaryotic translation initiation factor 4E (eIF-4E), which possesses cap-binding activity, functions in the recruitment of mRNA to polysomes as part of a three-subunit complex, eIF-4F (cap-binding complex)...
  8. Wheater M, Johnson P, Blaydes J. The role of MNK proteins and eIF4E phosphorylation in breast cancer cell proliferation and survival. Cancer Biol Ther. 2010;10:728-35 pubmed publisher
    b>eIF4E is over-expressed in many tumours, including a high proportion of breast cancers. eIF4E is an oncogene, and signalling pathways which promote eIF4E activity represent potential targets for therapeutic intervention in cancer...
  9. Topisirovic I, Siddiqui N, Lapointe V, Trost M, Thibault P, Bangeranye C, et al. Molecular dissection of the eukaryotic initiation factor 4E (eIF4E) export-competent RNP. EMBO J. 2009;28:1087-98 pubmed publisher
    The eukaryotic translation initiation factor 4E (eIF4E) controls gene expression through its effects on mRNA export and cap-dependent translation, both of which contribute to its oncogenic potential...

More Information

Publications67

  1. Cao J, He L, Lin G, Hu C, Dong R, Zhang J, et al. Cap-dependent translation initiation factor, eIF4E, is the target for Ouabain-mediated inhibition of HIF-1?. Biochem Pharmacol. 2014;89:20-30 pubmed publisher
    ..Basing on in silico, in vitro and ex vivo models of translation processing, further studies revealed that eIF4E plays a critical role in the inhibitory effect of Ouabain on HIF-1? protein synthesis, rather than mTORC1, eIF2? ..
  2. Yi T, Papadopoulos E, Hagner P, Wagner G. Hypoxia-inducible factor-1? (HIF-1?) promotes cap-dependent translation of selective mRNAs through up-regulating initiation factor eIF4E1 in breast cancer cells under hypoxia conditions. J Biol Chem. 2013;288:18732-42 pubmed publisher
    ..The eIF4E translation initiation factors, eIF4E1, eIF4E2, and eIF4E3, are essential for translation initiation...
  3. Culjkovic Kraljacic B, Baguet A, Volpon L, Amri A, Borden K. The oncogene eIF4E reprograms the nuclear pore complex to promote mRNA export and oncogenic transformation. Cell Rep. 2012;2:207-15 pubmed publisher
    The eukaryotic translation initiation factor eIF4E is a potent oncogene that promotes the nuclear export and translation of specific transcripts...
  4. Muta D, Makino K, Nakamura H, Yano S, Kudo M, Kuratsu J. Inhibition of eIF4E phosphorylation reduces cell growth and proliferation in primary central nervous system lymphoma cells. J Neurooncol. 2011;101:33-9 pubmed publisher
    The mRNA cap-binding protein eukaryotic initiation factor 4E (eIF4E) plays an important role in mRNA translation; its activity is implicated in cell growth and proliferation...
  5. 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. ..
  6. Yang S, Hewitt S, Steinberg S, Liewehr D, Swain S. Expression levels of eIF4E, VEGF, and cyclin D1, and correlation of eIF4E with VEGF and cyclin D1 in multi-tumor tissue microarray. Oncol Rep. 2007;17:281-7 pubmed
    The mRNA cap-binding protein, eukaryotic initiation factor 4E (eIF4E), is a rate-limiting factor of cap-dependent translation initiation...
  7. Dilling M, Germain G, Dudkin L, Jayaraman A, Zhang X, Harwood F, et al. 4E-binding proteins, the suppressors of eukaryotic initiation factor 4E, are down-regulated in cells with acquired or intrinsic resistance to rapamycin. J Biol Chem. 2002;277:13907-17 pubmed
    ..cells, as compared with parental cells, approximately 10-fold less 4E-binding protein (4E-BP) was bound to eIF4E, and total cellular 4E-BP was markedly reduced. Levels of eIF4E were unchanged...
  8. Cohen N, Sharma M, Kentsis A, Perez J, Strudwick S, Borden K. PML RING suppresses oncogenic transformation by reducing the affinity of eIF4E for mRNA. EMBO J. 2001;20:4547-59 pubmed
    ..We demonstrate that eukaryotic initiation factor 4E (eIF4E) directly binds the PML RING, a domain required for association with bodies and for suppression of transformation...
  9. Gingras A, Gygi S, Raught B, Polakiewicz R, Abraham R, Hoekstra M, et al. Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism. Genes Dev. 1999;13:1422-37 pubmed
    ..The eIF4F subunit eIF4E interacts directly with the mRNA 5' cap structure...
  10. Graff J, Konicek B, Vincent T, Lynch R, Monteith D, Weir S, et al. Therapeutic suppression of translation initiation factor eIF4E expression reduces tumor growth without toxicity. J Clin Invest. 2007;117:2638-48 pubmed
    Expression of eukaryotic translation initiation factor 4E (eIF4E) is commonly elevated in human and experimental cancers, promoting angiogenesis and tumor growth...
  11. Gorrini C, Loreni F, Gandin V, Sala L, Sonenberg N, Marchisio P, et al. Fibronectin controls cap-dependent translation through beta1 integrin and eukaryotic initiation factors 4 and 2 coordinated pathways. Proc Natl Acad Sci U S A. 2005;102:9200-5 pubmed
    ..These findings indicate that integrins may recruit the translational machinery in a unique way and that FN-dependent translation cannot be blocked by mammalian target of rapamycin inhibition. ..
  12. Wu M, Liu Y, Di X, Kang H, Zeng H, Zhao Y, et al. EIF4E over-expresses and enhances cell proliferation and cell cycle progression in nasopharyngeal carcinoma. Med Oncol. 2013;30:400 pubmed publisher
    b>Eukaryotic translation initiation factor 4E (eIF4E) is involved in integration and amplification of many carcinogenesis signals in tumors...
  13. Carroll M, Borden K. The oncogene eIF4E: using biochemical insights to target cancer. J Interferon Cytokine Res. 2013;33:227-38 pubmed publisher
    The eukaryotic translation initiation factor eIF4E is overexpressed in many human malignancies where it is typically a harbinger of poor prognosis. eIF4E is positioned as a nexus in post-transcriptional gene expression...
  14. Shih J, Wang W, Tsai T, Kuo C, Li H, Wu Lee Y. Critical roles of RNA helicase DDX3 and its interactions with eIF4E/PABP1 in stress granule assembly and stress response. Biochem J. 2012;441:119-29 pubmed publisher
    ..However, its role in SG physiology remains undefined. We have demonstrated previously that DDX3 acts as an eIF4E (eukaryotic initiation factor 4E)-inhibitory protein to suppress translation...
  15. Fierro Monti I, Mohammed S, Matthiesen R, Santoro R, Burns J, Williams D, et al. Quantitative proteomics identifies Gemin5, a scaffolding protein involved in ribonucleoprotein assembly, as a novel partner for eukaryotic initiation factor 4E. J Proteome Res. 2006;5:1367-78 pubmed
    ..Components and proteins associated with the translation initiation eIF4F complex that may affect complex formation were identified and quantitated under distinct growth conditions...
  16. Patel M, Jay Dixon J, Sadiq A, Jacobson B, Kratzke R. Resistance to EGFR-TKI can be mediated through multiple signaling pathways converging upon cap-dependent translation in EGFR-wild type NSCLC. J Thorac Oncol. 2013;8:1142-7 pubmed publisher
    ..Finally, using an antisense oligonucleotide against eukaryotic translation initiation factor 4E and a small-molecule inhibitor to disrupt eIF4F formation, we show that cap-dependent ..
  17. Waskiewicz A, Johnson J, Penn B, Mahalingam M, Kimball S, Cooper J. Phosphorylation of the cap-binding protein eukaryotic translation initiation factor 4E by protein kinase Mnk1 in vivo. Mol Cell Biol. 1999;19:1871-80 pubmed
    b>Eukaryotic translation initiation factor 4E (eIF4E) binds to the mRNA 5' cap and brings the mRNA into a complex with other protein synthesis initiation factors and ribosomes...
  18. Culjkovic B, Topisirovic I, Borden K. Controlling gene expression through RNA regulons: the role of the eukaryotic translation initiation factor eIF4E. Cell Cycle. 2007;6:65-9 pubmed
    The eukaryotic translation initiation factor eIF4E is a potent oncogene. In fact, its overexpression in human cancer often correlates with poor prognosis...
  19. Marcotrigiano J, Gingras A, Sonenberg N, Burley S. Cap-dependent translation initiation in eukaryotes is regulated by a molecular mimic of eIF4G. Mol Cell. 1999;3:707-16 pubmed
    eIF4G uses a conserved Tyr-X-X-X-X-Leu-phi segment (where X is variable and phi is hydrophobic) to recognize eIF4E during cap-dependent translation initiation in eukaryotes...
  20. Pons B, Peg V, Vázquez Sánchez M, López Vicente L, Argelaguet E, Coch L, et al. The effect of p-4E-BP1 and p-eIF4E on cell proliferation in a breast cancer model. Int J Oncol. 2011;39:1337-45 pubmed publisher
    ..4E-BP1 and the eIF4F complex regulate cap-dependent translation...
  21. Jacobson B, De A, Kratzke M, Patel M, Jay Dixon J, Whitson B, et al. Activated 4E-BP1 represses tumourigenesis and IGF-I-mediated activation of the eIF4F complex in mesothelioma. Br J Cancer. 2009;101:424-31 pubmed publisher
    ..stimulation resulted in the activation of the cap-mediated translation complex as indicated by an increased eIF4G/eIF4E ratio in cap-affinity assays. Akt inhibition reversed the eIF4G/eIF4E ratio...
  22. 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
    ..Among the repertoire of proteins present in SGs is eukaryotic initiation factor 4E (eIF4E), a translation factor required for cap-dependent translation and that regulates a rate-limiting step for protein ..
  23. Topisirovic I, Capili A, Borden K. Gamma interferon and cadmium treatments modulate eukaryotic initiation factor 4E-dependent mRNA transport of cyclin D1 in a PML-dependent manner. Mol Cell Biol. 2002;22:6183-98 pubmed
    The eukaryotic initiation factor 4E (eIF4E), when dysregulated, transforms cells. A substantial fraction of eIF4E forms nuclear bodies that colocalize with those associated with the promyelocytic leukemia protein PML...
  24. Abiko F, Tomoo K, Mizuno A, Morino S, Imataka H, Ishida T. Binding preference of eIF4E for 4E-binding protein isoform and function of eIF4E N-terminal flexible region for interaction, studied by SPR analysis. Biochem Biophys Res Commun. 2007;355:667-72 pubmed
    To investigate the binding preference of eIF4E for the three eIF4E-binding isoforms (4E-BP1-3) and the function of N-terminal flexible region of eIF4E for their interactions, the binding parameters of recombinant full-length and N-..
  25. Poulin F, Gingras A, Olsen H, Chevalier S, Sonenberg N. 4E-BP3, a new member of the eukaryotic initiation factor 4E-binding protein family. J Biol Chem. 1998;273:14002-7 pubmed
    ..The cap is recognized by eukaryotic initiation factor 4F (eIF4F), which consists of three polypeptides, including eIF4E, the cap-binding protein subunit...
  26. Norton K, McClusky D, Sen S, Yu H, Meschonat C, Debenedetti A, et al. TLK1B is elevated with eIF4E overexpression in breast cancer. J Surg Res. 2004;116:98-103 pubmed
    The overexpression of eukaryotic initiation factor 4E (eIF4E), a critical component of the "RNA helicase" necessary for the initiation of protein synthesis of mRNAs with long 5' prime untranslated regions (5'UTRs), can result ..
  27. Hariri F, Arguello M, Volpon L, Culjkovic Kraljacic B, Nielsen T, Hiscott J, et al. The eukaryotic translation initiation factor eIF4E is a direct transcriptional target of NF-?B and is aberrantly regulated in acute myeloid leukemia. Leukemia. 2013;27:2047-55 pubmed publisher
    The eukaryotic translation initiation factor eIF4E is a potent oncogene elevated in many cancers, including the M4 and M5 subtypes of acute myeloid leukemia (AML)...
  28. Andrei M, Ingelfinger D, Heintzmann R, Achsel T, Rivera Pomar R, Luhrmann R. A role for eIF4E and eIF4E-transporter in targeting mRNPs to mammalian processing bodies. RNA. 2005;11:717-27 pubmed
    ..We demonstrate that human P bodies contain the cap-binding protein eIF4E and the related factor eIF4E-transporter (eIF4E-T), suggesting novel roles for these proteins in targeting mRNAs ..
  29. Fan S, Ramalingam S, Kauh J, Xu Z, Khuri F, Sun S. Phosphorylated eukaryotic translation initiation factor 4 (eIF4E) is elevated in human cancer tissues. Cancer Biol Ther. 2009;8:1463-9 pubmed
    b>Eukaryotic translation initiation factor 4E (eIF4E) is a rate-limiting factor for cap-dependent protein synthesis and is regulated by PI3 kinase/mTOR and mitogen-activated protein kinase (MAPK)/Mnk signaling pathways...
  30. Ilic N, Utermark T, Widlund H, Roberts T. PI3K-targeted therapy can be evaded by gene amplification along the MYC-eukaryotic translation initiation factor 4E (eIF4E) axis. Proc Natl Acad Sci U S A. 2011;108:E699-708 pubmed publisher
    ..Importantly, either MYC or eukaryotic translation initiation factor 4E (eIF4E) was required to bypass pharmacological PI3K/mTOR inhibition in resistant cells...
  31. Imataka H, Sonenberg N. Human eukaryotic translation initiation factor 4G (eIF4G) possesses two separate and independent binding sites for eIF4A. Mol Cell Biol. 1997;17:6940-7 pubmed
    Mammalian translation initiation factor 4F (eIF4F) consists of three subunits, eIF4A, eIF4E, and eIF4G. eIF4G interacts directly with both eIF4A and eIF4E...
  32. Topisirovic I, Culjkovic B, Cohen N, Perez J, Skrabanek L, Borden K. The proline-rich homeodomain protein, PRH, is a tissue-specific inhibitor of eIF4E-dependent cyclin D1 mRNA transport and growth. EMBO J. 2003;22:689-703 pubmed
    The translation initiation factor eIF4E is involved in the modulation of cellular growth...
  33. Topisirovic I, Guzman M, McConnell M, Licht J, Culjkovic B, Neering S, et al. Aberrant eukaryotic translation initiation factor 4E-dependent mRNA transport impedes hematopoietic differentiation and contributes to leukemogenesis. Mol Cell Biol. 2003;23:8992-9002 pubmed
    The eukaryotic translation initiation factor 4E (eIF4E) acts as both a key translation factor and as a promoter of nucleocytoplasmic transport of specific transcripts...
  34. Liang S, Guo R, Zhang Z, Liu D, Xu H, Xu Z, et al. Upregulation of the eIF4E signaling pathway contributes to the progression of gastric cancer, and targeting eIF4E by perifosine inhibits cell growth. Oncol Rep. 2013;29:2422-30 pubmed publisher
    The increase of eukaryotic translation initiation factor 4E (eIF4E) expression is frequently observed in several types of cancer, making eIF4E an attractive anticancer drug target...
  35. Li Y, Yue P, Deng X, Ueda T, Fukunaga R, Khuri F, et al. Protein phosphatase 2A negatively regulates eukaryotic initiation factor 4E phosphorylation and eIF4F assembly through direct dephosphorylation of Mnk and eIF4E. Neoplasia. 2010;12:848-55 pubmed
    The eukaryotic translation initiation factor 4E (eIF4E) is frequently overexpressed in human cancers and is associated with cellular transformation, tumorigenesis, and metastatic progression. It is known that Mnks can phosphorylate eIF4E...
  36. Zhou S, Wang G, Liu C, Zhou M. Eukaryotic initiation factor 4E (eIF4E) and angiogenesis: prognostic markers for breast cancer. BMC Cancer. 2006;6:231 pubmed
    The overexpression of eukaryotic translation initiation factor 4E (eIF4E), a key regulator of protein synthesis, is involved in the malignant progression of human breast cancer...
  37. Berkel H, Turbat Herrera E, Shi R, De Benedetti A. Expression of the translation initiation factor eIF4E in the polyp-cancer sequence in the colon. Cancer Epidemiol Biomarkers Prev. 2001;10:663-6 pubmed
    The eukaryotic translation initiation factor 4E (eIF4E) has been shown to play a key role in cell growth, and several studies have documented an increased expression of eIF4E in a number of solid tumors, including breast, bladder, ..
  38. Waskiewicz A, Flynn A, Proud C, Cooper J. Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2. EMBO J. 1997;16:1909-20 pubmed
    ..MNK1 may define a convergence point between the growth factor-activated and one of the stress-activated protein kinase cascades and is a candidate to phosphorylate eIF-4E in cells. ..
  39. Suzuki Y, Minami M, Suzuki M, Abe K, Zenno S, Tsujimoto M, et al. The Hsp90 inhibitor geldanamycin abrogates colocalization of eIF4E and eIF4E-transporter into stress granules and association of eIF4E with eIF4G. J Biol Chem. 2009;284:35597-604 pubmed publisher
    The eukaryotic translation initiation factor eIF4E plays a critical role in the control of translation initiation through binding to the mRNA 5' cap structure...
  40. Stead R, Proud C. Rapamycin enhances eIF4E phosphorylation by activating MAP kinase-interacting kinase 2a (Mnk2a). FEBS Lett. 2013;587:2623-8 pubmed publisher
    Eukaryotic initiation factor eIF4E and its phosphorylation play key roles in cell transformation and tumorigenesis. eIF4E is phosphorylated by the Mnks (MAP (mitogen-activated protein) kinase-interacting kinases)...
  41. Adesso L, Calabretta S, Barbagallo F, Capurso G, Pilozzi E, Geremia R, et al. Gemcitabine triggers a pro-survival response in pancreatic cancer cells through activation of the MNK2/eIF4E pathway. Oncogene. 2013;32:2848-57 pubmed publisher
    ..we aimed at investigating the involvement of the mitogen activating protein kinase interacting kinase (MNK)/eIF4E pathway in the acquired drug resistance of PDAC cells...
  42. Fournier M, Coudert L, Mellaoui S, Adjibade P, Gareau C, Côté M, et al. Inactivation of the mTORC1-eukaryotic translation initiation factor 4E pathway alters stress granule formation. Mol Cell Biol. 2013;33:2285-301 pubmed publisher
    ..Here, we report a novel role of the mTORC1-eukaryotic translation initiation factor 4E (eIF4E) pathway, a key regulator of cap-dependent translation initiation of oncogenic factors, ..
  43. Xu X, Vatsyayan J, Gao C, Bakkenist C, Hu J. Sumoylation of eIF4E activates mRNA translation. EMBO Rep. 2010;11:299-304 pubmed publisher
    b>Eukaryotic translation initiation factor 4E (eIF4E) is the cap-binding protein that binds the 5' cap structure of cellular messenger RNAs (mRNAs)...
  44. Rufener S, Mühlemann O. eIF4E-bound mRNPs are substrates for nonsense-mediated mRNA decay in mammalian cells. Nat Struct Mol Biol. 2013;20:710-7 pubmed publisher
    ..kinetics of two NMD reporter genes in mRNA fractions bound to either CBC or the eukaryotic initiation factor 4E (eIF4E) in human cells and demonstrate that NMD destabilizes eIF4E-bound transcripts as efficiently as those associated ..
  45. Durand S, Lykke Andersen J. Nonsense-mediated mRNA decay occurs during eIF4F-dependent translation in human cells. Nat Struct Mol Biol. 2013;20:702-9 pubmed publisher
    ..initiated on mRNAs associated with the cap-binding complex (CBC) and that the exchange of the CBC for the eIF4F translation initiation complex renders mRNAs immune to NMD...
  46. Khoury T, Alrawi S, Ramnath N, Li Q, Grimm M, Black J, et al. Eukaryotic initiation factor-4E and cyclin D1 expression associated with patient survival in lung cancer. Clin Lung Cancer. 2009;10:58-66 pubmed publisher
    Eukaryotic initiation factor 4E (eIF4E) and cyclin D1, two important factors in cell-cycle progression, play key roles in the carcinogenesis of varied human cancers...
  47. Kentsis A, Dwyer E, Perez J, Sharma M, Chen A, Pan Z, et al. The RING domains of the promyelocytic leukemia protein PML and the arenaviral protein Z repress translation by directly inhibiting translation initiation factor eIF4E. J Mol Biol. 2001;312:609-23 pubmed
    ..to directly interact, with sub-micromolar affinity, with the dorsal surface of translation initiation factor eIF4E, representing a novel mode of eIF4E recognition...
  48. Connolly E, Braunstein S, Formenti S, Schneider R. Hypoxia inhibits protein synthesis through a 4E-BP1 and elongation factor 2 kinase pathway controlled by mTOR and uncoupled in breast cancer cells. Mol Cell Biol. 2006;26:3955-65 pubmed
    ..Breast cancer cells therefore acquire resistance to hypoxia by uncoupling oxygen-responsive signaling pathways from mTOR function, eliminating inhibition of protein synthesis mediated by 4E-BP1 and eEF2. ..
  49. Nathan C, Amirghahari N, Abreo F, Rong X, Caldito G, Jones M, et al. Overexpressed eIF4E is functionally active in surgical margins of head and neck cancer patients via activation of the Akt/mammalian target of rapamycin pathway. Clin Cancer Res. 2004;10:5820-7 pubmed
    Overexpression of eIF4E in surgical margins of head and neck cancer patients is an independent risk factor for recurrence...
  50. Uniacke J, Holterman C, Lachance G, Franovic A, Jacob M, Fabian M, et al. An oxygen-regulated switch in the protein synthesis machinery. Nature. 2012;486:126-9 pubmed publisher
    ..The initial step of protein synthesis is the binding of the eukaryotic translation initiation factor 4E (eIF4E) to the 7-methylguanosine (m(7)-GpppG) 5'?cap of messenger RNAs...
  51. Culjkovic B, Topisirovic I, Skrabanek L, Ruiz Gutierrez M, Borden K. eIF4E is a central node of an RNA regulon that governs cellular proliferation. J Cell Biol. 2006;175:415-26 pubmed
    This study demonstrates that the eukaryotic translation initiation factor eIF4E is a critical node in an RNA regulon that impacts nearly every stage of cell cycle progression...
  52. Xu X, Vatsyayan J, Gao C, Bakkenist C, Hu J. HDAC2 promotes eIF4E sumoylation and activates mRNA translation gene specifically. J Biol Chem. 2010;285:18139-43 pubmed publisher
    ..show that HDAC2 is also involved in cap-dependent mRNA translation by promoting sumoylation of eukaryotic translation initiation factor 4E (eIF4E), which is independent of its deacetylase activity...
  53. Kiriakidou M, Tan G, Lamprinaki S, De Planell Saguer M, Nelson P, Mourelatos Z. An mRNA m7G cap binding-like motif within human Ago2 represses translation. Cell. 2007;129:1141-51 pubmed
    ..MC) within the Mid domain of Ago proteins, which bears significant similarity to the m(7)G cap-binding domain of eIF4E, an essential translation initiation factor...
  54. Graff J, Konicek B, Lynch R, Dumstorf C, Dowless M, McNulty A, et al. eIF4E activation is commonly elevated in advanced human prostate cancers and significantly related to reduced patient survival. Cancer Res. 2009;69:3866-73 pubmed publisher
    Elevated eukaryotic translation initiation factor 4E (eIF4E) function induces malignancy in experimental models by selectively enhancing translation of key malignancy-related mRNAs (c-myc and BCL-2)...
  55. Zhu N, Gu L, Findley H, Zhou M. Transcriptional repression of the eukaryotic initiation factor 4E gene by wild type p53. Biochem Biophys Res Commun. 2005;335:1272-9 pubmed
    The eukaryotic initiation factor 4E (eIF4E) plays important roles in transformation and cancer progression. It is frequently overexpressed in malignant cells, one mechanism of which is through transcriptional activation by c-myc...
  56. Pyronnet S, Imataka H, Gingras A, Fukunaga R, Hunter T, Sonenberg N. Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to phosphorylate eIF4E. EMBO J. 1999;18:270-9 pubmed
    Human eukaryotic translation initiation factor 4E (eIF4E) binds to the mRNA cap structure and interacts with eIF4G, which serves as a scaffold protein for the assembly of eIF4E and eIF4A to form the eIF4F complex...
  57. Lim S, Saw T, Zhang M, Janes M, Nacro K, Hill J, et al. Targeting of the MNK-eIF4E axis in blast crisis chronic myeloid leukemia inhibits leukemia stem cell function. Proc Natl Acad Sci U S A. 2013;110:E2298-307 pubmed publisher
    ..Here, we show that the MAP kinase interacting serine/threonine kinase (MNK)-eukaryotic translation initiation factor 4E (eIF4E) axis is overexpressed in BC GMPs but not normal HSCs, and that MNK kinase-dependent ..
  58. Wichroski M, Robb G, Rana T. Human retroviral host restriction factors APOBEC3G and APOBEC3F localize to mRNA processing bodies. PLoS Pathog. 2006;2:e41 pubmed
    ..a ribonucleoprotein complex with other P-body proteins which have established roles in cap-dependent translation (eIF4E and eIF4E-T), translation suppression (RCK/p54), RNA interference-mediated post-transcriptional gene silencing (..