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Gene Review

Eif4e  -  eukaryotic translation initiation factor 4E

Mus musculus

Synonyms: EG668879, Eif4e-ps, Eukaryotic translation initiation factor 4E, If4e, eIF-4E, ...
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Disease relevance of Eif4e


High impact information on Eif4e

  • The translation factor eIF-4E promotes tumor formation and cooperates with c-Myc in lymphomagenesis [6].
  • Our results implicate activation of eIF-4E as a key event in oncogenic transformation by phosphoinositide-3 kinase and Akt [6].
  • We have shown previously that overexpression of eIF-4E in rodent fibroblasts results in tumorigenic transformation. eIF-4E also exhibits mitogenic activity when microinjected into serum-starved NIH-3T3 cells [7].
  • This inhibition is causally related to the dephosphorylation and consequent activation of 4E-BP1, a protein recently identified as a repressor of the cap-binding protein, eIF-4E, function [8].
  • This effect may represent one mechanism by which eIF-4E regulates cell growth and transforms cells in culture [9].

Biological context of Eif4e


Anatomical context of Eif4e

  • However, neither general protein synthesis nor cap-dependent translation, as assayed by a bicistronic reporter assay system, was affected in Mnk-deficient embryonic fibroblasts, despite the absence of phosphorylated eIF4E [11].
  • Insulin and IGF-I increased the amount of eIF4G associated with eIF4E in nutrient-deprived C2C12 myotubes [14].
  • Overexpression of eIF4E rendered polysome recruitment of mRNAs with structured 5' untranslated regions largely independent of growth factor and resistant to the PI3K inhibitor LY294002 [15].
  • Overexpression of eIF4E did not induce factor-independent growth but specifically impaired differentiation into mature erythrocytes [15].
  • Here we show that either serum treatment or activation of the stress-activated protein kinase (JNK/SAPK) led to enhanced phosphorylation of eIF4E in quiescent NIH 3T3 cells [16].

Associations of Eif4e with chemical compounds

  • In Mnk1-Mnk2 DKO mice, no phosphorylated eIF4E was detected in any tissue studied, even after LPS or insulin injection [11].
  • Removal of tetracycline induced eIF4E expression up to fivefold over endogenous levels [12].
  • The association constant values of recombinant eIF4E for 20 different cap analogues cover six orders of magnitude; with the highest affinity observed for m(7)GTP (approximately 1.1 x 10(8) M(-1)) [17].
  • In addition, overexpression of eIF4E rendered progenitors insensitive to the differentiation-inducing effect of LY294002, indicating that control of mRNA translation is a major pathway downstream of PI3K in the regulation of progenitor expansion [15].
  • The amount of serine 1108-phosphorylated eIF4G (but not Ser209-phosphorylated eIF4E) was induced following PH [18].

Physical interactions of Eif4e


Enzymatic interactions of Eif4e

  • Strikingly, upon induction of eIF4E, 4E-BP1 became dephosphorylated and the extent of dephosphorylation was proportional to the expression level of eIF4E [12].

Regulatory relationships of Eif4e


Other interactions of Eif4e


Analytical, diagnostic and therapeutic context of Eif4e


  1. Acute treatment with TNF-alpha attenuates insulin-stimulated protein synthesis in cultures of C2C12 myotubes through a MEK1-sensitive mechanism. Williamson, D.L., Kimball, S.R., Jefferson, L.S. Am. J. Physiol. Endocrinol. Metab. (2005) [Pubmed]
  2. Identifying mRNA subsets in messenger ribonucleoprotein complexes by using cDNA arrays. Tenenbaum, S.A., Carson, C.C., Lager, P.J., Keene, J.D. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  3. c-Jun NH2-Terminal Kinase 2{alpha}2 Promotes the Tumorigenicity of Human Glioblastoma Cells. Cui, J., Han, S.Y., Wang, C., Su, W., Harshyne, L., Holgado-Madruga, M., Wong, A.J. Cancer Res. (2006) [Pubmed]
  4. The eukaryotic translation initiation factor 4E is not modified during the course of vaccinia virus replication. Gierman, T.M., Frederickson, R.M., Sonenberg, N., Pickup, D.J. Virology (1992) [Pubmed]
  5. Proto oncogene/eukaryotic translation initiation factor (eIF) 4E attenuates mevalonate-mediated regulation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase synthesis. Buechler, R.D., Peffley, D.M. Mol. Carcinog. (2004) [Pubmed]
  6. The translation factor eIF-4E promotes tumor formation and cooperates with c-Myc in lymphomagenesis. Ruggero, D., Montanaro, L., Ma, L., Xu, W., Londei, P., Cordon-Cardo, C., Pandolfi, P.P. Nat. Med. (2004) [Pubmed]
  7. Ras mediates translation initiation factor 4E-induced malignant transformation. Lazaris-Karatzas, A., Smith, M.R., Frederickson, R.M., Jaramillo, M.L., Liu, Y.L., Kung, H.F., Sonenberg, N. Genes Dev. (1992) [Pubmed]
  8. Rapamycin blocks the phosphorylation of 4E-BP1 and inhibits cap-dependent initiation of translation. Beretta, L., Gingras, A.C., Svitkin, Y.V., Hall, M.N., Sonenberg, N. EMBO J. (1996) [Pubmed]
  9. mRNAs containing extensive secondary structure in their 5' non-coding region translate efficiently in cells overexpressing initiation factor eIF-4E. Koromilas, A.E., Lazaris-Karatzas, A., Sonenberg, N. EMBO J. (1992) [Pubmed]
  10. Alcohol acceptance, preference, and sensitivity in mice. II. Quantitative trait loci mapping analysis using BXD recombinant inbred strains. Rodriguez, L.A., Plomin, R., Blizard, D.A., Jones, B.C., McClearn, G.E. Alcohol. Clin. Exp. Res. (1995) [Pubmed]
  11. Mnk2 and Mnk1 are essential for constitutive and inducible phosphorylation of eukaryotic initiation factor 4E but not for cell growth or development. Ueda, T., Watanabe-Fukunaga, R., Fukuyama, H., Nagata, S., Fukunaga, R. Mol. Cell. Biol. (2004) [Pubmed]
  12. Translational homeostasis: eukaryotic translation initiation factor 4E control of 4E-binding protein 1 and p70 S6 kinase activities. Khaleghpour, K., Pyronnet, S., Gingras, A.C., Sonenberg, N. Mol. Cell. Biol. (1999) [Pubmed]
  13. Exercise-induced alterations in extracellular signal-regulated kinase 1/2 and mammalian target of rapamycin (mTOR) signalling to regulatory mechanisms of mRNA translation in mouse muscle. Williamson, D.L., Kubica, N., Kimball, S.R., Jefferson, L.S. J. Physiol. (Lond.) (2006) [Pubmed]
  14. Insulin and IGF-I stimulate the formation of the eukaryotic initiation factor 4F complex and protein synthesis in C2C12 myotubes independent of availability of external amino acids. Shen, W.H., Boyle, D.W., Wisniowski, P., Bade, A., Liechty, E.A. J. Endocrinol. (2005) [Pubmed]
  15. Translation initiation factor 4E inhibits differentiation of erythroid progenitors. Blázquez-Domingo, M., Grech, G., von Lindern, M. Mol. Cell. Biol. (2005) [Pubmed]
  16. Involvement of stress-activated protein kinase and p38/RK mitogen-activated protein kinase signaling pathways in the enhanced phosphorylation of initiation factor 4E in NIH 3T3 cells. Morley, S.J., McKendrick, L. J. Biol. Chem. (1997) [Pubmed]
  17. Biophysical studies of eIF4E cap-binding protein: recognition of mRNA 5' cap structure and synthetic fragments of eIF4G and 4E-BP1 proteins. Niedzwiecka, A., Marcotrigiano, J., Stepinski, J., Jankowska-Anyszka, M., Wyslouch-Cieszynska, A., Dadlez, M., Gingras, A.C., Mak, P., Darzynkiewicz, E., Sonenberg, N., Burley, S.K., Stolarski, R. J. Mol. Biol. (2002) [Pubmed]
  18. Rapamycin-sensitive induction of eukaryotic initiation factor 4F in regenerating mouse liver. Goggin, M.M., Nelsen, C.J., Kimball, S.R., Jefferson, L.S., Morley, S.J., Albrecht, J.H. Hepatology (2004) [Pubmed]
  19. The eIF4E-binding proteins 1 and 2 are negative regulators of cell growth. Rousseau, D., Gingras, A.C., Pause, A., Sonenberg, N. Oncogene (1996) [Pubmed]
  20. 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. Lin, T.A., Kong, X., Saltiel, A.R., Blackshear, P.J., Lawrence, J.C. J. Biol. Chem. (1995) [Pubmed]
  21. Cell cycle progression and proliferation despite 4BP-1 dephosphorylation. Marx, S.O., Marks, A.R. Mol. Cell. Biol. (1999) [Pubmed]
  22. Initiation of mRNA translation in oncogenesis: the role of eIF4E. Montanaro, L., Pandolfi, P.P. Cell Cycle (2004) [Pubmed]
  23. Eukaryotic translation initiation factor 4E regulates expression of cyclin D1 at transcriptional and post-transcriptional levels. Rosenwald, I.B., Kaspar, R., Rousseau, D., Gehrke, L., Leboulch, P., Chen, J.J., Schmidt, E.V., Sonenberg, N., London, I.M. J. Biol. Chem. (1995) [Pubmed]
  24. Erythropoietin stimulates phosphorylation of eIF-4E and identification of a 37-kD phosphoprotein that binds mRNA caps in erythroblasts. Bu, X., Bondurant, M.C., Hagedorn, C.H. Exp. Hematol. (1996) [Pubmed]
  25. High affinity RNA for mammalian initiation factor 4E interferes with mRNA-cap binding and inhibits translation. Mochizuki, K., Oguro, A., Ohtsu, T., Sonenberg, N., Nakamura, Y. RNA (2005) [Pubmed]
  26. Increased expression of eukaryotic translation initiation factors eIF-4E and eIF-2 alpha in response to growth induction by c-myc. Rosenwald, I.B., Rhoads, D.B., Callanan, L.D., Isselbacher, K.J., Schmidt, E.V. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  27. Positive heat capacity change upon specific binding of translation initiation factor eIF4E to mRNA 5' cap. Niedzwiecka, A., Stepinski, J., Darzynkiewicz, E., Sonenberg, N., Stolarski, R. Biochemistry (2002) [Pubmed]
  28. Cap-binding activity of an eIF4E homolog from Leishmania. Yoffe, Y., Zuberek, J., Lewdorowicz, M., Zeira, Z., Keasar, C., Orr-Dahan, I., Jankowska-Anyszka, M., Stepinski, J., Darzynkiewicz, E., Shapira, M. RNA (2004) [Pubmed]
  29. Overexpressing eukaryotic translation initiation factor 4E stimulates bovine mammary epithelial cell proliferation. Long, E., Lazaris-Karatzas, A., Karatzas, C., Zhao, X. Int. J. Biochem. Cell Biol. (2001) [Pubmed]
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