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Gene Review

EIF4G1  -  eukaryotic translation initiation factor 4...

Homo sapiens

Synonyms: EIF-4G1, EIF4F, EIF4G, EIF4GI, Eukaryotic translation initiation factor 4 gamma 1, ...
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Disease relevance of EIF4G1

  • Paip2 preferentially inhibits translation of a poly(A)-containing mRNA, but has no effect on the translation of hepatitis C virus mRNA, which is cap- and eIF4G-independent [1].
  • In vivo, 100k protein displaces Mnk1 from eIF4G during adenovirus infection, or in transfected cells [2].
  • Poliovirus infection engenders the cleavage of the eIF4G (formerly p220) component of eIF4F and renders this complex inactive for cap-dependent translation [3].
  • In contrast, EMCV infection does not result in eIF4G cleavage [3].
  • A 49-amino-acid region of eIF-4 gamma, located in the N-terminal side of the site of cleavage by Picornaviridae protease 2A, was found to be sufficient for interacting with eIF-4E [4].

High impact information on EIF4G1


Chemical compound and disease context of EIF4G1


Biological context of EIF4G1


Anatomical context of EIF4G1

  • Tethering of eIF4G to adenoviral mRNAs by viral 100k protein drives ribosome shunting [17].
  • While eIF4G stably associates with spliceosomes in vitro and shows close association with spliceosomal snRNPs and splicing factors in vivo, depletion studies show that it does not participate directly in the splicing reaction [18].
  • Preferential translation of heat shock mRNAs in HeLa cells deficient in protein synthesis initiation factors eIF-4E and eIF-4 gamma [19].
  • Interaction of eIF4G with poly(A)-binding protein stimulates translation and is critical for Xenopus oocyte maturation [20].
  • In the reticulocyte lysate, eIF4G unable to interact directly with PABP showed little impairment in its ability to support translation, whereas loss of either of the eIF4A-binding sites or the eIF3-binding site resulted in a marked decrease in activity [21].

Associations of EIF4G1 with chemical compounds

  • In this work, we demonstrate that the expression of the amino-terminal one-third of eIF4G, which interacts with eIF4E and PABP, in Xenopus oocyte inhibits translation and progesterone-induced maturation [22].
  • The NH2- and COOH-terminal fragments of eIF-4 gamma were separated by reverse phase HPLC and identified with specific antibodies, and the NH2-terminal sequence of the COOH-terminal fragment was determined by automated Edman degradation [23].
  • For example, eIF4G and eIF4E-binding proteins (4E-BPs) modulate cap affinity, and thus physiological activity of eIF4E, by binding a site distal to the 7-methylguanosine cap-binding site [24].
  • Sucrose gradient sedimentation studies demonstrated that eIF-4 gamma was present on both 43 and 48 S initiation complexes but not 80 S complexes [25].
  • Analysis of p220 from control and okadaic acid-treated cells demonstrated serine and threonine phosphorylation under both conditions [26].

Physical interactions of EIF4G1

  • Here, we report that the pioneer round, which can be assessed by measuring NMD, is not inhibited by 4E-BP1, which is known to inhibit steady-state translation by competing with eIF4G for binding to eIF4E [27].
  • In mammals, however, there has been no evidence that eIF4G binds PABP [14].
  • A mutant adenovirus with a temperature-sensitive 100k protein that cannot inhibit cellular protein synthesis at restrictive temperature no longer blocks Mnk1 binding to eIF4G, or phosphorylation of eIF4E [2].
  • Several eIF4A mutants showing wild-type level binding to Pdcd4 were also inactivated for binding to eIF4G and for enhancing translation [28].
  • We demonstrate that all four AUF1 protein isoforms bind directly and strongly to initiation factor eIF4G at a C-terminal site regardless of AUF1 interaction with the ARE [29].

Enzymatic interactions of EIF4G1

  • However, it was suggested that in poliovirus infection, the 2Apro induces the activation of a cellular proteinase which in turn cleaves eIF4G [30].
  • Second, infusion of TNF-alpha for 24 h in control rats resulted in a 70% decrease in phosphorylated eIF4G [31].

Regulatory relationships of EIF4G1

  • RNA interference releases Pak2-induced inhibition of translation in contact-inhibited cells by 2.7-fold. eIF4G mutants of the Pak2 site show that S896D inhibits translation, while S896A has no effect [32].
  • The availability of eIF4E for binding to eIF4G is regulated by the phosphorylation of a small family of eIF4E-binding proteins (the 4E-BPs) [33].
  • These data indicate that SLBP stimulates the translation of histone mRNAs through a functional interaction with both the mRNA stem-loop and the 5' cap that is mediated by eIF4G and eIF3 [34].
  • Studies with the specific inhibitor, SB203580, have shown that signalling through the p38 MAP kinase pathway is not required for either the Fas/CD95-induced cleavage of eIF4G or cell death [35].
  • Here, we report that based on antibody and mRNA reporter injection assays, maskin prevents oocyte maturation and the translation of the CPE-containing cyclin B1 mRNA by blocking the association of eIF4G with eIF4E [36].

Other interactions of EIF4G1

  • Overexpression of Hsc70, a constitutive homolog of Hsp70, prevented loss of cap-initiation complexes and maintained eIF4G solubility [37].
  • 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 [38].
  • Here we report that Mnk1 is associated with the eIF4F complex via its interaction with the C-terminal region of eIF4G [13].
  • The N-terminal part of DAP-5 has 39% identity and 63% similarity to the central region of mammalian p220 [39].
  • Here, we present evidence that eIF4G and the large subunit of the nuclear cap-binding complex, CBP80, share a common origin and domain structure [40].

Analytical, diagnostic and therapeutic context of EIF4G1


  1. Translational repression by a novel partner of human poly(A) binding protein, Paip2. Khaleghpour, K., Svitkin, Y.V., Craig, A.W., DeMaria, C.T., Deo, R.C., Burley, S.K., Sonenberg, N. Mol. Cell (2001) [Pubmed]
  2. Adenovirus-specific translation by displacement of kinase Mnk1 from cap-initiation complex eIF4F. Cuesta, R., Xi, Q., Schneider, R.J. EMBO J. (2000) [Pubmed]
  3. Activation of the translational suppressor 4E-BP1 following infection with encephalomyocarditis virus and poliovirus. Gingras, A.C., Svitkin, Y., Belsham, G.J., Pause, A., Sonenberg, N. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  4. 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. Mader, S., Lee, H., Pause, A., Sonenberg, N. Mol. Cell. Biol. (1995) [Pubmed]
  5. eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation. Gingras, A.C., Raught, B., Sonenberg, N. Annu. Rev. Biochem. (1999) [Pubmed]
  6. Small-Molecule Inhibition of the Interaction between the Translation Initiation Factors eIF4E and eIF4G. Moerke, N.J., Aktas, H., Chen, H., Cantel, S., Reibarkh, M.Y., Fahmy, A., Gross, J.D., Degterev, A., Yuan, J., Chorev, M., Halperin, J.A., Wagner, G. Cell (2007) [Pubmed]
  7. Recognition of the rotavirus mRNA 3' consensus by an asymmetric NSP3 homodimer. Deo, R.C., Groft, C.M., Rajashankar, K.R., Burley, S.K. Cell (2002) [Pubmed]
  8. Interaction of polyadenylate-binding protein with the eIF4G homologue PAIP enhances translation. Craig, A.W., Haghighat, A., Yu, A.T., Sonenberg, N. Nature (1998) [Pubmed]
  9. Proteolysis of the p220 component of the cap-binding protein complex is not sufficient for complete inhibition of host cell protein synthesis after poliovirus infection. Bonneau, A.M., Sonenberg, N. J. Virol. (1987) [Pubmed]
  10. Monensin and nigericin prevent the inhibition of host translation by poliovirus, without affecting p220 cleavage. Irurzun, A., Sánchez-Palomino, S., Novoa, I., Carrasco, L. J. Virol. (1995) [Pubmed]
  11. Hybrid proteins between Pseudomonas aeruginosa exotoxin A and poliovirus 2Apro cleave p220 in HeLa cells. Novoa, I., Cotten, M., Carrasco, L. J. Virol. (1996) [Pubmed]
  12. Leader protein of encephalomyocarditis virus binds zinc, is phosphorylated during viral infection, and affects the efficiency of genome translation. Dvorak, C.M., Hall, D.J., Hill, M., Riddle, M., Pranter, A., Dillman, J., Deibel, M., Palmenberg, A.C. Virology (2001) [Pubmed]
  13. Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to phosphorylate eIF4E. Pyronnet, S., Imataka, H., Gingras, A.C., Fukunaga, R., Hunter, T., Sonenberg, N. EMBO J. (1999) [Pubmed]
  14. A newly identified N-terminal amino acid sequence of human eIF4G binds poly(A)-binding protein and functions in poly(A)-dependent translation. Imataka, H., Gradi, A., Sonenberg, N. EMBO J. (1998) [Pubmed]
  15. Structural basis for competitive inhibition of eIF4G-Mnk1 interaction by the adenovirus 100-kilodalton protein. Cuesta, R., Xi, Q., Schneider, R.J. J. Virol. (2004) [Pubmed]
  16. Overproduction of a conserved domain of fission yeast and mammalian translation initiation factor eIF4G causes aberrant cell morphology and results in disruption of the localization of F-actin and the organization of microtubules. Hashemzadeh-Bonehi, L., Curtis, P.S., Morley, S.J., Thorpe, J.R., Pain, V.M. Genes Cells (2003) [Pubmed]
  17. Tethering of eIF4G to adenoviral mRNAs by viral 100k protein drives ribosome shunting. Xi, Q., Cuesta, R., Schneider, R.J. Genes Dev. (2004) [Pubmed]
  18. Interaction of eukaryotic translation initiation factor 4G with the nuclear cap-binding complex provides a link between nuclear and cytoplasmic functions of the m(7) guanosine cap. McKendrick, L., Thompson, E., Ferreira, J., Morley, S.J., Lewis, J.D. Mol. Cell. Biol. (2001) [Pubmed]
  19. Preferential translation of heat shock mRNAs in HeLa cells deficient in protein synthesis initiation factors eIF-4E and eIF-4 gamma. Joshi-Barve, S., De Benedetti, A., Rhoads, R.E. J. Biol. Chem. (1992) [Pubmed]
  20. Interaction of eIF4G with poly(A)-binding protein stimulates translation and is critical for Xenopus oocyte maturation. Wakiyama, M., Imataka, H., Sonenberg, N. Curr. Biol. (2000) [Pubmed]
  21. Functional Analysis of Individual Binding Activities of the Scaffold Protein eIF4G. Hinton, T.M., Coldwell, M.J., Carpenter, G.A., Morley, S.J., Pain, V.M. J. Biol. Chem. (2007) [Pubmed]
  22. Inhibition of translation and progesterone-induced maturation of Xenopus oocytes by expressing the amino-terminal portion of the eukaryotic translation initiation factor 4G. Wakiyama, M., Miura, K. Biosci. Biotechnol. Biochem. (2002) [Pubmed]
  23. Mapping the cleavage site in protein synthesis initiation factor eIF-4 gamma of the 2A proteases from human Coxsackievirus and rhinovirus. Lamphear, B.J., Yan, R., Yang, F., Waters, D., Liebig, H.D., Klump, H., Kuechler, E., Skern, T., Rhoads, R.E. J. Biol. Chem. (1993) [Pubmed]
  24. Cap-free structure of eIF4E suggests a basis for conformational regulation by its ligands. Volpon, L., Osborne, M.J., Topisirovic, I., Siddiqui, N., Borden, K.L. EMBO J. (2006) [Pubmed]
  25. In vitro synthesis of human protein synthesis initiation factor 4 gamma and its localization on 43 and 48 S initiation complexes. Joshi, B., Yan, R., Rhoads, R.E. J. Biol. Chem. (1994) [Pubmed]
  26. Novel phosphorylation sites of eukaryotic initiation factor-4F and evidence that phosphorylation stabilizes interactions of the p25 and p220 subunits. Bu, X., Haas, D.W., Hagedorn, C.H. J. Biol. Chem. (1993) [Pubmed]
  27. The pioneer translation initiation complex is functionally distinct from but structurally overlaps with the steady-state translation initiation complex. Chiu, S.Y., Lejeune, F., Ranganathan, A.C., Maquat, L.E. Genes Dev. (2004) [Pubmed]
  28. Mutational analysis of the DEAD-box RNA helicase eIF4AII characterizes its interaction with transformation suppressor Pdcd4 and eIF4GI. Zakowicz, H., Yang, H.S., Stark, C., Wlodawer, A., Laronde-Leblanc, N., Colburn, N.H. RNA (2005) [Pubmed]
  29. Assembly of AUF1 with eIF4G-poly(A) binding protein complex suggests a translation function in AU-rich mRNA decay. Lu, J.Y., Bergman, N., Sadri, N., Schneider, R.J. RNA (2006) [Pubmed]
  30. The eIF4G-eIF4E complex is the target for direct cleavage by the rhinovirus 2A proteinase. Haghighat, A., Svitkin, Y., Novoa, I., Kuechler, E., Skern, T., Sonenberg, N. J. Virol. (1996) [Pubmed]
  31. Cytokine-triggered decreases in levels of phosphorylated eukaryotic initiation factor 4g in skeletal muscle during sepsis. Vary, T.C., Deiter, G., Lang, C.H. Shock (2006) [Pubmed]
  32. Inhibition of cap-dependent translation via phosphorylation of eIF4G by protein kinase Pak2. Ling, J., Morley, S.J., Traugh, J.A. EMBO J. (2005) [Pubmed]
  33. Targets and mechanisms for the regulation of translation in malignant transformation. Clemens, M.J. Oncogene (2004) [Pubmed]
  34. The histone 3'-terminal stem-loop-binding protein enhances translation through a functional and physical interaction with eukaryotic initiation factor 4G (eIF4G) and eIF3. Ling, J., Morley, S.J., Pain, V.M., Marzluff, W.F., Gallie, D.R. Mol. Cell. Biol. (2002) [Pubmed]
  35. Cleavage of translation initiation factor 4G (eIF4G) during anti-Fas IgM-induced apoptosis does not require signalling through the p38 mitogen-activated protein (MAP) kinase. Morley, S.J., McKendrick, L., Bushell, M. FEBS Lett. (1998) [Pubmed]
  36. Dissolution of the maskin-eIF4E complex by cytoplasmic polyadenylation and poly(A)-binding protein controls cyclin B1 mRNA translation and oocyte maturation. Cao, Q., Richter, J.D. EMBO J. (2002) [Pubmed]
  37. Chaperone hsp27 inhibits translation during heat shock by binding eIF4G and facilitating dissociation of cap-initiation complexes. Cuesta, R., Laroia, G., Schneider, R.J. Genes Dev. (2000) [Pubmed]
  38. Repression of cap-dependent translation by 4E-binding protein 1: competition with p220 for binding to eukaryotic initiation factor-4E. Haghighat, A., Mader, S., Pause, A., Sonenberg, N. EMBO J. (1995) [Pubmed]
  39. DAP-5, a novel homolog of eukaryotic translation initiation factor 4G isolated as a putative modulator of gamma interferon-induced programmed cell death. Levy-Strumpf, N., Deiss, L.P., Berissi, H., Kimchi, A. Mol. Cell. Biol. (1997) [Pubmed]
  40. eIF4G and CBP80 share a common origin and similar domain organization: implications for the structure and function of eIF4G. Marintchev, A., Wagner, G. Biochemistry (2005) [Pubmed]
  41. Recognition of eIF4G by rotavirus NSP3 reveals a basis for mRNA circularization. Groft, C.M., Burley, S.K. Mol. Cell (2002) [Pubmed]
  42. A single amino acid change in protein synthesis initiation factor 4G renders cap-dependent translation resistant to picornaviral 2A proteases. Lamphear, B.J., Rhoads, R.E. Biochemistry (1996) [Pubmed]
  43. Human protein synthesis initiation factor eIF-4 gamma is encoded by a single gene (EIF4G) that maps to chromosome 3q27-qter. Yan, R., Rhoads, R.E. Genomics (1995) [Pubmed]
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