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Gene Review

Eif4e  -  eukaryotic translation initiation factor 4E

Rattus norvegicus

Synonyms: Eukaryotic translation initiation factor 4E, eIF-4E, eIF-4F 25 kDa subunit, eIF4E, mRNA cap-binding protein
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Disease relevance of Eif4e


Psychiatry related information on Eif4e

  • In summary, these data suggest that chronic alcohol consumption impairs translation initiation in muscle by altering multiple regulatory sites, including eIF2B activity and eIF4E availability [6].
  • We have recently shown that reducing the protein levels of eIF-4E in CREF T24 (AS4E line) markedly decreases soft-agar colonization, increases tumor latency periods and increases tumor doubling times without significantly altering monolayer growth [7].

High impact information on Eif4e

  • This subunit is present in limiting amounts in the cell, and is thought to be regulated by phosphorylation: decreased phosphorylation of eIF-4E following various treatments correlates with a decrease in cellular translation rate [8].
  • We report here that overexpression of eIF-4E in NIH 3T3 and Rat 2 fibroblasts causes their tumorigenic transformation as determined by three criteria: formation of transformed foci on a monolayer of cells; anchorage-independent growth; and tumour formation in nude mice [8].
  • These observations suggest that eIF-4E lies on the mitogenic signal transduction pathway, and we reasoned that overexpression of eIF-4E might profoundly affect cellular growth properties [8].
  • Nonphosphorylated PHAS-I bound to initiation factor 4E (eIF-4E) and inhibited protein synthesis [9].
  • Because the release of eIF4E from its binding protein as a result of phosphorylation is followed by formation of a messenger RNA cap-binding complex that includes the initiation factor eIF4G, we evaluated the association of eIF4G with released eIF4E and showed that it was increased by CCK [10].

Chemical compound and disease context of Eif4e


Biological context of Eif4e


Anatomical context of Eif4e


Associations of Eif4e with chemical compounds


Physical interactions of Eif4e

  • Additionally, rapamycin prevented the stimulatory effects of leucine on eIF4E availability for binding eIF4G and inhibited leucine-dependent phosphorylation of S6K1 [18].
  • Increased availability of eIF4E occurred as a consequence of diminished abundance of the inactive 4E-BP1.eIF4E complex following IGF-I [19].

Regulatory relationships of Eif4e


Other interactions of Eif4e


Analytical, diagnostic and therapeutic context of Eif4e


  1. Oxidant stress stimulates phosphorylation of eIF4E without an effect on global protein synthesis in smooth muscle cells. Lack of evidence for a role of H202 in angiotensin II-induced hypertrophy. Rao, G.N. J. Biol. Chem. (2000) [Pubmed]
  2. Diminished ERK 1/2 and p38 MAPK phosphorylation in skeletal muscle during sepsis. Vary, T.C., Deiter, G., Lang, C.H. Shock (2004) [Pubmed]
  3. Cellular energy status modulates translational control mechanisms in ischemic-reperfused rat hearts. Crozier, S.J., Vary, T.C., Kimball, S.R., Jefferson, L.S. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
  4. Hypoxia increases the association of 4E-binding protein 1 with the initiation factor 4E in isolated rat hepatocytes. Tinton, S.A., Buc-Calderon, P.M. FEBS Lett. (1999) [Pubmed]
  5. The intraischemic and early reperfusion changes of protein synthesis in the rat brain. eIF-2 alpha kinase activity and role of initiation factors eIF-2 alpha and eIF-4E. Burda, J., Martín, M.E., Gottlieb, M., Chavko, M., Marsala, J., Alcázar, A., Pavón, M., Fando, J.L., Salinas, M. J. Cereb. Blood Flow Metab. (1998) [Pubmed]
  6. Inhibition of muscle protein synthesis by alcohol is associated with modulation of eIF2B and eIF4E. Lang, C.H., Wu, D., Frost, R.A., Jefferson, L.S., Kimball, S.R., Vary, T.C. Am. J. Physiol. (1999) [Pubmed]
  7. Reduction of translation initiation factor 4E decreases the malignancy of ras-transformed cloned rat embryo fibroblasts. Graff, J.R., Boghaert, E.R., De Benedetti, A., Tudor, D.L., Zimmer, C.C., Chan, S.K., Zimmer, S.G. Int. J. Cancer (1995) [Pubmed]
  8. Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 5' cap. Lazaris-Karatzas, A., Montine, K.S., Sonenberg, N. Nature (1990) [Pubmed]
  9. PHAS-I as a link between mitogen-activated protein kinase and translation initiation. Lin, T.A., Kong, X., Haystead, T.A., Pause, A., Belsham, G., Sonenberg, N., Lawrence, J.C. Science (1994) [Pubmed]
  10. Regulation of the initiation of pancreatic digestive enzyme protein synthesis by cholecystokinin in rat pancreas in vivo. Bragado, M.J., Tashiro, M., Williams, J.A. Gastroenterology (2000) [Pubmed]
  11. Mnk1 is required for angiotensin II-induced protein synthesis in vascular smooth muscle cells. Ishida, M., Ishida, T., Nakashima, H., Miho, N., Miyagawa, K., Chayama, K., Oshima, T., Kambe, M., Yoshizumi, M. Circ. Res. (2003) [Pubmed]
  12. Eukaryotic initiation factor 4E degradation during brain ischemia. Neumar, R.W., DeGracia, D.J., White, B.C., McDermott, P.J., Evans, D.R., Krause, G.S. J. Neurochem. (1995) [Pubmed]
  13. Activated eIF4E-binding protein slows G1 progression and blocks transformation by c-myc without inhibiting cell growth. Lynch, M., Fitzgerald, C., Johnston, K.A., Wang, S., Schmidt, E.V. J. Biol. Chem. (2004) [Pubmed]
  14. Ischaemia induces changes in the association of the binding protein 4E-BP1 and eukaryotic initiation factor (eIF) 4G to eIF4E in differentiated PC12 cells. Martín, M.E., Muñoz, F.M., Salinas, M., Fando, J.L. Biochem. J. (2000) [Pubmed]
  15. Translation factor eIF4E rescues cells from Myc-dependent apoptosis by inhibiting cytochrome c release. Li, S., Takasu, T., Perlman, D.M., Peterson, M.S., Burrichter, D., Avdulov, S., Bitterman, P.B., Polunovsky, V.A. J. Biol. Chem. (2003) [Pubmed]
  16. A potential role for extracellular signal-regulated kinases in prostaglandin F2alpha-induced protein synthesis in smooth muscle cells. Rao, G.N., Madamanchi, N.R., Lele, M., Gadiparthi, L., Gingras, A.C., Eling, T.E., Sonenberg, N. J. Biol. Chem. (1999) [Pubmed]
  17. A role for PYK2 in ANG II-dependent regulation of the PHAS-1-eIF4E complex by multiple signaling cascades in vascular smooth muscle. Rocic, P., Jo, H., Lucchesi, P.A. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  18. Leucine stimulates translation initiation in skeletal muscle of postabsorptive rats via a rapamycin-sensitive pathway. Anthony, J.C., Yoshizawa, F., Anthony, T.G., Vary, T.C., Jefferson, L.S., Kimball, S.R. J. Nutr. (2000) [Pubmed]
  19. IGF-I activates the eIF4F system in cardiac muscle in vivo. Vary, T.C., Lang, C.H. Mol. Cell. Biochem. (2005) [Pubmed]
  20. Angiotensin II stimulates phosphorylation of the translational repressor 4E-binding protein 1 by a mitogen-activated protein kinase-independent mechanism. Fleurent, M., Gingras, A.C., Sonenberg, N., Meloche, S. J. Biol. Chem. (1997) [Pubmed]
  21. Phospholipase Cgamma-Erk Axis in vascular endothelial growth factor-induced eukaryotic initiation factor 4E phosphorylation and protein synthesis in renal epithelial cells. Mariappan, M.M., Senthil, D., Natarajan, K.S., Choudhury, G.G., Kasinath, B.S. J. Biol. Chem. (2005) [Pubmed]
  22. Transforming growth factor-alpha attenuates N-methyl-D-aspartic acid toxicity in cortical cultures by preventing protein synthesis inhibition through an Erk1/2-dependent mechanism. Petegnief, V., Friguls, B., Sanfeliu, C., Suñol, C., Planas, A.M. J. Biol. Chem. (2003) [Pubmed]
  23. Abundant expression of translation initiation factor EIF-4E in post-meiotic germ cells of the rat testis. Miyagi, Y., Kerr, S., Sugiyama, A., Asai, A., Shibuya, M., Fujimoto, H., Kuchino, Y. Lab. Invest. (1995) [Pubmed]
  24. Transcriptional regulation of the rat eIF4E gene in cardiac muscle cells: the role of specific elements in the promoter region. Makhlouf, A.A., Namboodiri, A.M., McDermott, P.J. Gene (2001) [Pubmed]
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