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Gene Review

CDC33  -  translation initiation factor eIF4E

Saccharomyces cerevisiae S288c

Synonyms: Eukaryotic translation initiation factor 4E, TIF45, YOL139C, eIF-4E, eIF-4F 25 kDa subunit, ...
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Disease relevance of CDC33

  • We describe a simple and rapid purification scheme that can yield 2-5 micrograms of a homogenous and active preparation of eIF-4E from 1 ml of E. coli culture [1].
  • Messenger RNAs encoding chloramphenicol acetyltransferase (CAT) with or without the 5'-leader sequence of tobacco mosaic virus (TMV) RNA were synthesized in vitro and translated in Saccharomyces cerevisiae extracts dependent on eukaryotic initiation factors eIF-4E or eIF-4A [2].
  • This failure to bind correlated with resistance or reduced susceptibility, suggesting that interruption of the interaction between VPg and this eIF4E paralog may be necessary, but is not sufficient for potyvirus resistance in vivo [3].
  • Effective expression of the active eIF-4E was achieved in the soluble fraction of the insect cell Sf9, which was infected with the recombinant baculovirus [4].

High impact information on CDC33

  • It interacts with the small ribosomal subunit interacting protein, eIF3, and the eIF4E/cap-mRNA complex in order to load the ribosome onto mRNA during cap-dependent translation [5].
  • Cofolding allosterically enhances association of eIF4E with the cap and is required for maintenance of optimal growth and polysome distributions in vivo [5].
  • We find that Pab1p but not the cap binding protein eIF-4E is required for poly(A) tail-dependent translation, and that the Pab1p-poly(A) tail complex functions to recruit the 40S ribosomal subunit to the mRNA [6].
  • Using distinct vesicular transport mutants and chlorpromazine, we have identified the eIF2alpha kinase Gcn2p and the eIF4E binding protein Eap1p as major mediators of the translation attenuation response [7].
  • Here we report genetic and biochemical evidence that the yeast translation initiation factor eIF4G associates with CBC, and that eIF4E, the eIF4F component that binds both the cap and eIF4G, antagonizes this interaction [8].

Biological context of CDC33


Anatomical context of CDC33


Associations of CDC33 with chemical compounds


Physical interactions of CDC33

  • Specifically, we find that mutations which weaken the eIF4E binding site on the yeast eIF4G proteins Tif4631p and Tif4632p lead to temperature-sensitive growth in vivo and the stimulation of uncapped-mRNA translation in vitro [10].
  • High-copy expression of a mutant eIF4G defective for eIF4E binding resulted in a dominant negative phenotype in an xrn1 mutant, indicating the importance of this interaction in an xrn1 mutant [20].
  • NMD can trigger decay during any round of translation and can target Cbc-bound or eIF-4E-bound transcripts [21].
  • The cap binding protein eIF-4E copurifies with Ebs1p in the absence of RNA, suggesting that the two proteins interact in vivo [22].
  • In yeast, EAP1 encodes a protein that binds eIF4E and inhibits cap-dependent translation in vitro [11] [13].

Regulatory relationships of CDC33

  • In addition, we demonstrate that in vivo a temperature-sensitive allele of eIF4E (cdc33-42) suppressed the decapping defect of a partial loss-of-function allele of DCP1 [23].
  • The mutagenized gene was reintroduced on a plasmid into S. cerevisiae cells having their only wild-type eIF-4E gene on a plasmid under the control of the regulatable GAL1 promoter [17].
  • This suggests that serum stimulates the interaction between eIF4G and PABP by a distinct mechanism that is independent of both the mTOR pathway and the enhanced association of eIF4G with eIF4E [24].

Other interactions of CDC33

  • These experiments indicated that eIF4E is an inhibitor of Dcp1p in vitro due to its ability to bind the 5' cap structure [23].
  • This lengthened 5'-untranslated region likely reduces translation efficiency and down-regulates CLN3 protein synthesis, thereby correcting for the excess translation promoted by elevated Cdc33 [11].
  • Thus, the inhibition of mRNA turnover by blocking Xrn1p function does not suppress the lethality of defects upstream in the turnover pathway but it does enhance the requirement for (7)mG caps and for proper formation of the eIF4E/eIF4G cap recognition complex [20].
  • A cdc33-1 strain expressing either stable Cln3p (Cln3-1p) or a hybrid UBI4 5'-CLN3 mRNA, whose translation displays decreased dependence on eIF4E, arrested randomly in the cell cycle [25].
  • Another allele of CDC33, cdc33-1, along with mutations in CEG1, encoding the nuclear guanylyltransferase, were also synthetic lethal with xrn1Delta, whereas mutations in PRT1, encoding a subunit of eIF3, were not [20].

Analytical, diagnostic and therapeutic context of CDC33


  1. High-level synthesis in Escherichia coli of functional cap-binding eukaryotic initiation factor eIF-4E and affinity purification using a simplified cap-analog resin. Edery, I., Altmann, M., Sonenberg, N. Gene (1988) [Pubmed]
  2. The 5'-leader sequence of tobacco mosaic virus RNA mediates initiation-factor-4E-independent, but still initiation-factor-4A-dependent translation in yeast extracts. Altmann, M., Blum, S., Wilson, T.M., Trachsel, H. Gene (1990) [Pubmed]
  3. The pvr1 locus in Capsicum encodes a translation initiation factor eIF4E that interacts with Tobacco etch virus VPg. Kang, B.C., Yeam, I., Frantz, J.D., Murphy, J.F., Jahn, M.M. Plant J. (2005) [Pubmed]
  4. Expression of Xenopus laevis translation initiation factor 4E (eIF-4E) by baculovirus-insect cell system. Miyoshi, H., Ito, K., Sakai, N., Mizushima, J., Okamoto, K., Hori, H., Nishino, T., Wakiyama, M., Miura, K. Nucleic Acids Symp. Ser. (1997) [Pubmed]
  5. Ribosome loading onto the mRNA cap is driven by conformational coupling between eIF4G and eIF4E. Gross, J.D., Moerke, N.J., von der Haar, T., Lugovskoy, A.A., Sachs, A.B., McCarthy, J.E., Wagner, G. Cell (2003) [Pubmed]
  6. A common function for mRNA 5' and 3' ends in translation initiation in yeast. Tarun, S.Z., Sachs, A.B. Genes Dev. (1995) [Pubmed]
  7. A membrane transport defect leads to a rapid attenuation of translation initiation in Saccharomyces cerevisiae. Deloche, O., de la Cruz, J., Kressler, D., Doère, M., Linder, P. Mol. Cell (2004) [Pubmed]
  8. The yeast nuclear cap binding complex can interact with translation factor eIF4G and mediate translation initiation. Fortes, P., Inada, T., Preiss, T., Hentze, M.W., Mattaj, I.W., Sachs, A.B. Mol. Cell (2000) [Pubmed]
  9. Sequence analysis of a 9873 bp fragment of the left arm of yeast chromosome XV that contains the ARG8 and CDC33 genes, a putative riboflavin synthase beta chain gene, and four new open reading frames. Casas, C., Aldea, M., Casamayor, A., Lafuente, M.J., Gamo, F.J., Gancedo, C., Ariño, J., Herrero, E. Yeast (1995) [Pubmed]
  10. Binding of eukaryotic translation initiation factor 4E (eIF4E) to eIF4G represses translation of uncapped mRNA. Tarun, S.Z., Sachs, A.B. Mol. Cell. Biol. (1997) [Pubmed]
  11. Overexpression of eIF4E in Saccharomyces cerevisiae causes slow growth and decreased alpha-factor response through alterations in CLN3 expression. Anthony, C., Zong, Q., De Benedetti, A. J. Biol. Chem. (2001) [Pubmed]
  12. Efficient translation of an SSA1-derived heat-shock mRNA in yeast cells limited for cap-binding protein and eIF-4F. Barnes, C.A., MacKenzie, M.M., Johnston, G.C., Singer, R.A. Mol. Gen. Genet. (1995) [Pubmed]
  13. Yeast Eap1p, an eIF4E-associated protein, has a separate function involving genetic stability. Chial, H.J., Stemm-Wolf, A.J., McBratney, S., Winey, M. Curr. Biol. (2000) [Pubmed]
  14. Translational regulation of ribonucleotide reductase by eukaryotic initiation factor 4E links protein synthesis to the control of DNA replication. Abid, M.R., Li, Y., Anthony, C., De Benedetti, A. J. Biol. Chem. (1999) [Pubmed]
  15. Mutants of eukaryotic initiation factor eIF-4E with altered mRNA cap binding specificity reprogram mRNA selection by ribosomes in Saccharomyces cerevisiae. Vasilescu, S., Ptushkina, M., Linz, B., Müller, P.P., McCarthy, J.E. J. Biol. Chem. (1996) [Pubmed]
  16. Polypeptide-dependent protein kinase from bakers' yeast. Yanagita, Y., Abdel-Ghany, M., Raden, D., Nelson, N., Racker, E. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  17. Translation in Saccharomyces cerevisiae: initiation factor 4E-dependent cell-free system. Altmann, M., Sonenberg, N., Trachsel, H. Mol. Cell. Biol. (1989) [Pubmed]
  18. Altered mRNA cap recognition activity of initiation factor 4E in the yeast cell cycle division mutant cdc33. Altmann, M., Trachsel, H. Nucleic Acids Res. (1989) [Pubmed]
  19. Interaction between yeast eukaryotic initiation factor eIF4E and mRNA 5' cap analogues differs from that for murine eIF4E. Kiraga-Motoszko, K., Stepinski, J., Niedzwiecka, A., Jemielity, J., Wszelaka-Rylik, M., Stolarski, R., Zielenkiewicz, W., Darzynkiewicz, E. Nucleosides Nucleotides Nucleic Acids (2003) [Pubmed]
  20. Inhibition of mRNA turnover in yeast by an xrn1 mutation enhances the requirement for eIF4E binding to eIF4G and for proper capping of transcripts by Ceg1p. Brown, J.T., Yang, X., Johnson, A.W. Genetics (2000) [Pubmed]
  21. Transcript selection and the recruitment of mRNA decay factors for NMD in Saccharomyces cerevisiae. Culbertson, M.R., Neeno-Eckwall, E. RNA (2005) [Pubmed]
  22. Ebs1p, a negative regulator of gene expression controlled by the Upf proteins in the yeast Saccharomyces cerevisiae. Ford, A.S., Guan, Q., Neeno-Eckwall, E., Culbertson, M.R. Eukaryotic Cell (2006) [Pubmed]
  23. mRNA decapping in yeast requires dissociation of the cap binding protein, eukaryotic translation initiation factor 4E. Schwartz, D.C., Parker, R. Mol. Cell. Biol. (2000) [Pubmed]
  24. The association of initiation factor 4F with poly(A)-binding protein is enhanced in serum-stimulated Xenopus kidney cells. Fraser, C.S., Pain, V.M., Morley, S.J. J. Biol. Chem. (1999) [Pubmed]
  25. CLN3 expression is sufficient to restore G1-to-S-phase progression in Saccharomyces cerevisiae mutants defective in translation initiation factor eIF4E. Danaie, P., Altmann, M., Hall, M.N., Trachsel, H., Helliwell, S.B. Biochem. J. (1999) [Pubmed]
  26. Cloning of CDC33: a gene essential for growth and sporulation which does not interfere with cAMP production in Saccharomyces cerevisiae. Verdier, J.M., Camonis, J.H., Jacquet, M. Yeast (1989) [Pubmed]
  27. Circularization of mRNA by eukaryotic translation initiation factors. Wells, S.E., Hillner, P.E., Vale, R.D., Sachs, A.B. Mol. Cell (1998) [Pubmed]
  28. Circular dichroism and fluorescence studies on protein synthesis initiation factor eIF-4E and two mutant forms from the yeast Saccharomyces cerevisiae. McCubbin, W.D., Edery, I., Altmann, M., Sonenberg, N., Kay, C.M. J. Biol. Chem. (1988) [Pubmed]
  29. Interactions of the eIF-4F subunits in the yeast Saccharomyces cerevisiae. Lanker, S., Müller, P.P., Altmann, M., Goyer, C., Sonenberg, N., Trachsel, H. J. Biol. Chem. (1992) [Pubmed]
  30. Suppression of a temperature-sensitive cdc33 mutation of yeast by a multicopy plasmid expressing a Drosophila ribosomal protein. Lavoie, C., Tam, R., Clark, M., Lee, H., Sonenberg, N., Lasko, P. J. Biol. Chem. (1994) [Pubmed]
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