Evolution of eIF4E-Interacting Proteins

  • Greco HernándezEmail author
  • Kathleen M. Gillespie
  • Tsvetan R. Bachvaroff
  • Rosemary Jagus
  • Cátia Igreja
  • Daniel Peter
  • Manuel Bulfoni
  • Bertrand Cosson


Most eukaryotic mRNAs are translated by a cap-dependent mechanism, which requires recognition of the 5′ cap structure of the mRNA by eIF4E. Due to its crucial role in translation, eIF4E is a major target of regulation. One of the most prominent mechanisms regulating eIF4E activity is through its interaction with numerous proteins termed eIF4E-interacting proteins (4E-IPs). By competing with eIF4G for eIF4E binding, 4E-IPs act in general as translational repressors, although additional functions have been described. In this chapter, we discuss recent functional, phylogenetic and structural evidence that throws light on the evolution of 4E-IPs and evolutionary recurring themes. Phylogenetic analysis suggests that the first identified 4E-IPs, the mammalian 4E-binding proteins (4E-BPs), appeared as a single-copy gene in the last common ancestor of Amoebozoa, Glaucocystophyta, Fungi and Metazoa. 4E-BP is found in all Metazoans except Nematoda. It is found in glaucocystophytes, but has been lost in Viridiplantae. It is lost in most fungi, although it can be found in basidiomycetes as well as some glomeromycetes and zygomycetes. 4E-BP has been duplicated in vertebrates with up to six cognates found. 4E-BP seems to be absent, not lost, in most protist lineages since it has not been found in lineages thought to be at the root of the eukaryotes. Additional 4E-IPs, unrelated to 4E-BP, evolved independently in a lineage-specific manner, perhaps by a process of molecular tinkering, i.e., by gene duplication of preexisting proteins from different cellular processes and later in evolution incorporated into translation. Multiple duplications of eIF4E during eukaryotic radiation might have contributed, to some extent, to 4E-IP’s evolution. Some 4E-IPs are shared by different taxa, such as the eIF4E transporter, neuroguidin and Maskin, which are present in Amoebozoa, some/all fungi and the metazoan lineages. Unique lineage-specific 4E-IPs have evolved independently in some taxonomic groups such as Eap1p and p20 in yeasts, SPN-2 in C. elegans and Bicoid in higher Dipterans. Neuroguidin is the only 4E-IP represented in all eukaryotic lineages. Despite the diversity in function, sequence and origin, recent studies have revealed that 4E-IPs exhibit common binding principles when complexed with eIF4E.


eIF4E 4E-BP 4E-IP Translation evolution Translation initiation Cap-dependent translation 



G.H. thanks the National Institute of Cancer (INCan), Mexico, and the National Council of Science and Technology (CONACyT, Mexico, grant no. 168154) for funding this work. B.C and M.B. acknowledge Université Sorbonne Paris Cité (USPC) for the Research Project 2014 grant and 2015 International Fellowship. R.J and T.B are supported by NIH R01ES021949-01 and NSF OCE1313888 to R.J. and Allen R. Place. K.G. was supported by a graduate fellowship from the NOAA-EPP-funded Living Marine Sciences Cooperative Science Center (LMRCSC), NA11SEC4810002.


  1. 1.
    Hinnebusch AG. Molecular mechanism of scanning and start codon selection in eukaryotes. Microbiol Mol Biol Rev. 2011;75:434–67.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Aitken CE, Lorsch JR. A mechanistic overview of translation initiation in eukaryotes. Nat Struct Mol Biol. 2012;19:568–76.CrossRefPubMedGoogle Scholar
  3. 3.
    Sonenberg N, Hinnebusch A. Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell. 2009;136:731–45.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Jackson RJ, Hellen CU, Pestova TV. The mechanism of eukaryotic translation initiation and principles of its regulation. Nat Rev Molec Cell Biol. 2010;11:113–27.CrossRefGoogle Scholar
  5. 5.
    Yanagiya A, Svitkin YV, Shibata S, Mikami S, Imataka H, Sonenberg N. Requirement of RNA binding of mammalian eukaryotic translation initiation factor 4GI (eIF4GI) for efficient interaction of eIF4E with the mRNA cap. Mol Cell Biol. 2009;29:1661–9.CrossRefPubMedGoogle Scholar
  6. 6.
    Lin TA, Kong X, Haystead TA, Pause A, Belsham G, Sonenberg N, Lawrence JC. PHAS-I as a link between mitogen-activated protein kinase and translation initiation. Science. 1994;266:653–6.CrossRefPubMedGoogle Scholar
  7. 7.
    Pause A, Belsham GJ, Gingras AC, Donzé O, Lin TA, Lawrence JC, Sonenberg N. Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5’-cap function. Nature. 1994;371:762–7.CrossRefPubMedGoogle Scholar
  8. 8.
    Poulin F, Gingras AC, 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.CrossRefPubMedGoogle Scholar
  9. 9.
    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 gammaand the translational repressors 4E-binding proteins. Mol Cell Biol. 1995;15:4990–7.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Marcotrigiano J, Gingras AC, Sonenberg N, Burley SK. Cap-dependent translation initiation in eukaryotes is regulated by a molecular mimic of eIF4G. Mol Cell. 1999;3:707–16.CrossRefPubMedGoogle Scholar
  11. 11.
    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.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Richter JD, Sonenberg N. Regulation of cap-dependent translation by eIF4E inhibitory proteins. Nature. 2005;433:477–80.CrossRefPubMedGoogle Scholar
  13. 13.
    Bah A, Vernon RM, Siddiqui Z, Krzeminski M, Muhandiram R, Zhao C, Sonenberg N, Kay LE, Forman-Kay JD. Folding of an intrinsically disordered protein by phosphorylation as a regulatory switch. Nature. 2015;519:106–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Dowling RJ, Topisirovic I, Fonseca BD, Sonenberg N. Dissecting the role of mTOR: lessons from mTOR inhibitors. Biochim Biophys Acta. 2010;1804:433–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Ma XM, Blenis J. Molecular mechanisms of mTOR-mediated translational control. Nat Rev Mol Cell Biol. 2009;10:307–18.CrossRefPubMedGoogle Scholar
  16. 16.
    Fonseca BD, Smith EM, Yelle N, Alain T, Bushell M, Pause A. The ever-evolving role of mTOR in translation. Semin Cell Dev Biol. 2014;36:102–12.CrossRefPubMedGoogle Scholar
  17. 17.
    Raught B, Gingras AC. Signaling to translation initiation. In: Mathews MB, Sonenberg N, Hershey JWB, editors. Translational control in biology and medicine. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press; 2007. p. 369–400.Google Scholar
  18. 18.
    Sonenberg N. eIF4E, the mRNA cap-binding protein: from basic discovery to translational research. Biochem Cell Biol. 2008;86:178–83.CrossRefPubMedGoogle Scholar
  19. 19.
    Thoreen CC, Chantranupong L, Keys HR, Wang T, Gray NS, Sabatini DM. A unifying model for mTORC1-mediated regulation of mRNA translation. Nature. 2012;485:109–13.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Rhoads RE. eIF4E: new family members, new binding partners, new roles. J Biol Chem. 2009;284:16711–5.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Kamenska A, Simpson C, Standart N. eIF4E-binding proteins: new factors, new locations, new roles. Biochem Soc Trans. 2014;42:1238–45.CrossRefPubMedGoogle Scholar
  22. 22.
    Hernández G, Altmann M, Lasko P. Origins and evolution of the mechanisms regulating translation initiation in eukaryotes. Trends Biochem Sci. 2010;35:63–73.CrossRefPubMedGoogle Scholar
  23. 23.
    Sonenberg N, Hinnebusch AG. New modes of translation control in development, behavior, and disease. Mol Cell. 2007;28:721–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Hernández G, Miron M, Han H, Liu N, Magescas J, Tettweiler G, Frank F, Siddiqui N, Sonenberg N, Lasko P. Mextli is a novel eukaryotic translation initiation factor 4E-binding protein that promotes translation in Drosophila melanogaster. Mol Cell Biol. 2013;33:2854–64.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Kamenska A, Lu WT, Kubacka D, Broomhead H, Minshall N, Bushell M, Standart N. Human 4E-T represses translation of bound mRNAs and enhances microRNA-mediated silencing. Nucleic Acids Res. 2014;42:3298–313.CrossRefPubMedGoogle Scholar
  26. 26.
    Robalino J, Joshi B, Fahrenkrug SC, Jagus R. Two zebrafish eIF4E family members are differentially expressed and functionally divergent. J Biol Chem. 2004;279:10532–41.CrossRefPubMedGoogle Scholar
  27. 27.
    Bernal A, Kimbrell DA. Drosophila Thor participates in host immune defence and conects a translational regulator with innate immunity. Proc Natl Acad Sci USA. 2000;97:6019–24.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Miron M, Verdu J, Lachance PE, Birnbaum MJ, Lasko P, Sonenberg N. The translational inhibitor 4E-BP is an effector of PI(3)K/Akt signaling and cell growth. Nat Cell Biol. 2001;3:596–601.CrossRefPubMedGoogle Scholar
  29. 29.
    Oulhen N, Boulben S, Bidinosti M, Morales J, Cormier P, Cosson B. A variant mimicking hyperphosphorylated 4E-BP inhibits protein synthesis in a sea urchin cell-free, cap-dependent translation system. PLoS ONE. 2009;4:e5070.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Salaün P, Pyronnet S, Morales J, Mulner-Lorillon O, Bellé R, Sonenberg N, Cormier P. eIF4E/4E-BP dissociation and 4E-BP degradation in the first mitotic division of the sea urchin embryo. Dev Biol. 2003;255:428–39.CrossRefPubMedGoogle Scholar
  31. 31.
    Jung MY, Lorenz L, Richter JD. Translational control by neuroguidin, a eukaryotic initiation factor 4E and CPEB binding protein. Mol Cell Biol. 2006;26:4277–87.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Gosselin P, Martineau Y, Morales J, Czjzek M, Glippa V, Gauffeny I, Morin E, Le Corguillé G, Pyronnet S, Cormier P, Cosson B. Tracking a refined eIF4E-binding motif reveals Angel1 as a new partner of eIF4E. Nucleic Acid Res. 2013;41:7783–92.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Cho PF, Gamberi C, Cho-Park YA, Cho-Park IB, Lasko P, Sonenberg N. Cap-dependent translational inhibition establishes two opposing morphogen gradients in Drosophila embryos. Curr Biol. 2006;16:2031–41.CrossRefGoogle Scholar
  34. 34.
    Altmann M, Schmitz N, Berset C, Trachsel H. A novel inhibitor of cap-dependent translation initiation in yeast: p20 competes with eIF4G for binding to eIF4E. EMBO J. 1997;16:1114–21.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    de la Cruz J, Iost I, Kressler D, Linder P. The p20 and Ded1 proteins have antagonistic roles in eIF4E-dependent translation in Saccharomyces cerevisiae. Proc Natl Acad Sci USA. 1997;94:5201–6.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Park YU, Hur H, Ka M, Kim J. Identification of translation regulation target genes during filamentous growth in S. cerevisiae: regulatory role of Caf20 and Dhh1. Eukaryotic Cell. 5:2120–7.Google Scholar
  37. 37.
    Ibrahimo S, Holmes LE, Ashe MP. Regulation of translation initiation by the yeast eIF4E binding proteins is required for the pseudohyphal response. Yeast. 2006;23:1075–88.CrossRefPubMedGoogle Scholar
  38. 38.
    Zinoviev A, Leger M, Wagner G, Shapira M. A novel 4E-interacting protein in Leishmania is involved in stage-specific translation pathways. Nucleic Acids Res. 2011;39:8404–15.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Fierro-Monti I, Mohammed S, Matthiesen R, Santoro R, Burns JS, Williams DJ, Proud CG, Kassem M, Jensen ON, Roepstorff P. 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.CrossRefPubMedGoogle Scholar
  40. 40.
    Piñeiro D, Fernandez-Chamorro J, Francisco-Velilla R, Martinez-Salas E. Gemin5: a multitasking RNA-binding protein involved in translation control. Biomolecules. 2015;5:528–44.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Cohen N, Sharma M, Kentsis A, Perez JM, Strudwick S, Borden KL. PML RING suppresses oncogenic transformation by reducing the affinity of eIF4E for mRNA. EMBO J. 2001;20:4547–59.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Kentsis A, Dwyer EC, Perez JM, Sharma M, Chen A, Pan ZQ, Borden KL. 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.CrossRefPubMedGoogle Scholar
  43. 43.
    Morita M, Ler LW, Fabian MR, Siddiqui N, Mullin M, Henderson VC, Alain TF. B.D., Karashchuk G, Bennett CF, Kabuta T, Higashi S, Larsson O, Topisirovic, I., Smith RJ, Gingras AC, Sonenberg N. A novel 4EHP-GIGYF2 translational repressor complex is essential for mammalian development. Mol Cell Biol. 2012;32:3585–93.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Napoli I, Mercaldo V, Boyl PP, Eleuteri B, Zalfa F, De Rubeis S, Di Marino D, Mohr E, Massimi M, Falconi M, Witke W, Costa-Mattioli M, Sonenberg N, Achsel TB. C. The fragile X syndrome protein represses activity-dependent transation through CYFIP1, a new 4E-BP. Cell. 2008;134:1042–54.CrossRefPubMedGoogle Scholar
  45. 45.
    Topisirovic I, Siddiqui N, Lapointe VL, Trost M, Thibault P, Bangeranye C, Piñol-Roma S, Borden KL. Molecular dissection of the eukaryotic initiation factor 4E export-competent RNP. EMBO J. 2009;28:1087–98.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Köhler F, Müller-Rischart AK, Conradt BR. S.G. The loss of LRPPRC function induces the mitochondrial unfolded protein response. Aging. 2015;7:701–17.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Topisirovic I, Culjkovic B, Cohen N, Perez JM, Skrabanek L, Borden KL. The prolin-rich homeodomain protein, PRH, is a tissue-specific inhibitor of eIF4E-dependent cyclin D1 mRNA transport and growth. EMBO J. 2003;22:689–703.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Topisirovic I, Kentsis A, Perez JM, Guzman ML, Jordan CT, Borden KL. Eukaryotic translation initiation factor 4E activity is modulated by HOXA9 at multiple levels. Mol Cell Biol. 2005;25:1100–12.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Yarunin A, Harris RE, Ashe MP, Ashe HL. Patterning of the Drosophila oocyte by a sequential translation repression program involving the d4EHP and Belle translational repressors. RNA Biol. 2011;8:904–12.CrossRefPubMedGoogle Scholar
  50. 50.
    Shih JW, Tsai TY, Chao CH, Lee YH. Candidate tumor suppressor DDX3 RNA helicase specifically represses cap-dependent translation by acting as an eIF4E inhibitory protein. Oncogene. 2008;24:700–14.CrossRefGoogle Scholar
  51. 51.
    Rosnerm A, Rinkevich B. The DDX3 subfamily of the DEAD box helicases: divergent roles as unveiled by studying different organisms and in vitro assays. Curr Med Chem. 2007;14:2517–25.CrossRefGoogle Scholar
  52. 52.
    Tarn WY, Chang TH. The current understanding of Ded1p/DDX3 homologs from yeast to human. RNA Biol. 2009;6:17–20.CrossRefPubMedGoogle Scholar
  53. 53.
    Nédélec S, Nédélec S, Foucher I, Brunet I, Bouillot C, Prochiantz A, Trembleau A. Emx2 homeodomain transcription factor interacts with eukaryotic translation initiation factor 4E (eIF4E) in the axons of olfactory sensory neurons. Proc Natl Acad Sci USA. 2004;101:10815–20.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Villaescusa JC, Buratti C, Penkov D, Mathiasen L, Planagumà J, Ferretti E, Blasi F. Cytoplasmic Prep1 interacts with 4EHP inhibiting Hoxb4 translation. PLoS ONE. 2009;4:e5213.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Longobardi E, Penkov D, Mateos D, De Florian G, Torres M, Blasi F. Biochemistry of the tale transcription factors PREP, MEIS, and PBX in vertebrates. Dev Dyn. 2014;243:59–75.CrossRefPubMedGoogle Scholar
  56. 56.
    Minshall N, Reiter MH, Weil D, Standart N. CPEB interacts with an ovary-specific eIF4E and 4E-T in early Xenopus oocytes. J Biol Chem. 2007;282:37389–401.CrossRefPubMedGoogle Scholar
  57. 57.
    Piccioni F, Zappavigna V, Verrotti AC. A cup full of functions. RNA Biol. 2005;2:125–8.CrossRefPubMedGoogle Scholar
  58. 58.
    Keyes LN, Spradling AC. The Drosophila gene fs(2)cup interacts with otu to define a cytoplasmic pathway required for the structure and function of germ-line chromosomes. Development. 1997;124:1419–31.PubMedGoogle Scholar
  59. 59.
    Dostie J, Ferraiuolo M, Pause A, Adam SA, Sonenberg N. A novel shuttling protein, 4E-T, mediates the nuclear import of the mRNA 5’ cap-binding protein, eIF4E. EMBO J. 2000;19:3142–56.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Ferraiuolo MA, Basak S, Dostie J, Murray EL, Schoenberg DR, Sonenberg N. A role for the eIF4E-binding protein 4E-T in P-body formation and mRNA decay. J Cell Biol. 2005;170:913–24.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Kubacka D, Kamenska A, Broomhead H, Minshall N, Darzynkiewicz E, Standart N. Investigating the consequences of eIF4E2 (4EHP) interaction with 4E-transporter on its cellular distribution in HeLa cells. PLoS ONE. 2013;8:e72761.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Iwasaki S, Kawamata T, Tomari Y. Drosophila Argonaute1 and Argonaute2 employ distinct mechanisms for translational repression. Mol Cell. 2009;34:58–67.CrossRefPubMedGoogle Scholar
  63. 63.
    Lee SK, Lee JS, Shin KS, Yoo SJ. Translation initiation factor 4E is regulated by cell death inhibitor, Diap1. Mol Cells. 2007;24:445–51.PubMedGoogle Scholar
  64. 64.
    Vasudevan D. Don Ryoo H. Regulation of cell death by IAPs and their Antagonists. Curr Top Dev Biol. 2015;114:185–208.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Robbins RM, Gbur SC, Beitel GJ. Non-canonical roles for Yorkie and Drosophila Inhibitor of Apoptosis 1 in epithelial tube size control. PLoS ONE. 2014;9:e101609.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Cosentino GP, Schmelzle T, Haghighat A, Helliwell SB, Hall MN, Sonenberg N. Eap1p, a novel eukaryotic translation initiation factor 4E-associated protein in Saccharomyces cerevisiae. Mol Cell Biol. 2000;20:4604–13.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Chial HJ, Stemm-Wolf AJ, McBratney S, Winey M. Yeast Eap1, an eIF4E-associated protein, has a separate function involving genetic stability. Curr Biol. 2000;10:1519–22.CrossRefPubMedGoogle Scholar
  68. 68.
    Deloche O, de la Cruz J, Kressler D, Doère M, Linder P. A membrane transport defect leads to a rapid attenuation of translation initiation in Saccharomyces cerevisiae. Mol Cell. 2004;13:357–66.CrossRefPubMedGoogle Scholar
  69. 69.
    Amiri A, Keiper BD, Kawasaki I, Fan Y, Kohara Y, Rhoads RE, Strome S. An isoform of eIF4E is a component of germ granules and is required for spermatogenesis in C. elegans. Development. 2001;128:3899–912.PubMedPubMedCentralGoogle Scholar
  70. 70.
    Wang JT, Seydoux G. P granules. Curr Biol. 2014;24:R637–8.CrossRefPubMedGoogle Scholar
  71. 71.
    Li W, DeBella LR, Guven-Ozkan T, Lin R, Rose L. An eIF4E-binding protein regulates katanin protein levels in C. elegans embryos. J Cell Biol. 2009;187:33–42.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Stebbins-Boaz B, Cao Q, de Moor CH, Mendez R, Richter JD. Maskin is a CPEB-associated factor that transiently interacts with eIF4E. Mol Cell. 1999;4:1017–27.CrossRefPubMedGoogle Scholar
  73. 73.
    O’Brien LL, Albee AJ, Liu L, Tao W, Dobrzyn P, Lizarraga SB, Wiese C. The Xenopus TACC homologue, maskin, functions in mitotic spindle assembly. Mol Biol Cell. 2005;16:2836–47.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Peset I, Seiler J, Sardon T, Bejarano LA, Rybina S, Vernos I. Function and regulation of Maskin, a TACC family protein, in microtubule growth during mitosis. J Cell Biol. 2005;170:1057–66.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Albee AJ, Wiese C. Xenopus TACC3/maskin is not required for microtubule stability but is required for anchoring microtubules at the centrosome. Mol Biol Cell. 2008;19:3347–56.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Kinoshita K, Noetzel TL, Pelletier L, Mechtler K, Drechsel DN, Schwager A, Lee MR. J.W., Hyman AA. Aurora A phosphorylation of TACC3/maskin is required for centrosome-dependent microtubule assembly in mitosis. J Cell Biol. 2005;170:1047–55.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Moury B, Charron C, Janzac B, Simon V, Gallois JL, Palloix A, Caranta C. Evolution of plant eukaryotic initiation factor 4E (eIF4E) and potyvirus genome-linked protein (VPg): a game of mirrors impacting resistance spectrum and durability. Infect Genet Evol. 2014;27:472–80.CrossRefPubMedGoogle Scholar
  78. 78.
    Jiang J, Laliberté JF. The genome-linked protein VPg of plant viruses-a protein with many partners. Curr Opin Virol. 2011;1:347–54.CrossRefPubMedGoogle Scholar
  79. 79.
    Goodfellow I. The genome-linked protein VPg of vertebrate viruses - a multifaceted protein. Curr Opin Virol. 2011;1:355–62.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Hernández G, Vazquez-Pianzola P. Functional diversity of the eukaryotic translation initiation factors belonging to eIF4 families. Mech Dev. 2005;122:865–76.CrossRefPubMedGoogle Scholar
  81. 81.
    Joshi B, Lee K, Maeder DL, Jagus R. Phylogenetic analysis of eIF4E-family members. BMC Evol Biol. 2005;5:48.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Patrick RM, Browning KS. The eIF4F and eIF(iso)4F complexes of plants: an evolutionary perspective. Comp Funct Genomics. 2012;2012:287814.CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Jones GD, Williams EP, Place AR, Jagus R, Bachvaroff TR. The alveolate translation initiation factor 4E family reveals a custom toolkit for translational control in core dinoflagellates. BMC Evol Biol. 2015;15:14.CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Tettweiler G, Kowanda M, Lasko P, Sonenberg N, Hernández G. The distribution of eIF4E-family members across insecta. Comp Funct Genom. 2012;2012:960420.CrossRefGoogle Scholar
  85. 85.
    Evsikov AV. Marín de Evsikova C. Evolutionary origin and phylogenetic analysis of the novel oocyte-specific eukaryotic translation initiation factor 4E in Tetrapoda. Dev Genes Evol. 2009;219:111–8.CrossRefPubMedGoogle Scholar
  86. 86.
    Jagus R, Bachvaroff TR, Joshi B, Place AR. Diversity of eukaryotic translational initiation factor eIF4E in protists. Comp Funct Genom. 2012;2012:134839.CrossRefGoogle Scholar
  87. 87.
    Laursen BS, Sørensen HP, Mortensen KK, Sperling-Petersen HU. Initiation of protein synthesis in bacteria. Microbiol Mol Biol Rev. 2005;69:101–23.CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Benelli D, Londei P. Begin at the beginning: evolution of translational initiation Res Microbiol. 2009;160:493–501.PubMedGoogle Scholar
  89. 89.
    Benelli D, Londei P. Translation initiation in Archaea: conserved and domain-specific features. Biochem Soc Trans. 2011;19:89–93.CrossRefGoogle Scholar
  90. 90.
    Londei P. Evolution of translational initiation: news insights from the archaea. FEMS Microbiol Rev. 2005;29:185–200.CrossRefPubMedGoogle Scholar
  91. 91.
    Hernández G. Was the initiation of translation in early eukaryotes IRES-driven? Trends Biochem Sci. 2008;33:58–64.CrossRefPubMedGoogle Scholar
  92. 92.
    Hernández G. On the origin of the cap-dependent initiation of translation in eukaryotes. Trends Biochem Sci. 2009;34:166–75.CrossRefPubMedGoogle Scholar
  93. 93.
    Aravind L, Koonin EV. Eukaryotic-specific domains in translation initiation factors: implications for translation regulation and evolution of the translation system. Genome Res. 2000;10:1172–84.CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Kyrpides NC, Woese CR. Universally conserved translation initiation factors. Proc Natl Acad Sci USA. 1998;95:224–8.CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Hernández G. On the emergence and evolution of the eukaryotic translation apparatus. In: Biyani M, editor. Cell-free protein synthesis. Rijekra, Croatia: InTech; 2012. p. 31–50.Google Scholar
  96. 96.
    Hernández G, Proud CG, Preiss T, Parsyan A. On the diversification of the translation apparatus across eukaryotes. Comp Funct Genom. 2012;2012:256848.Google Scholar
  97. 97.
    Marcotrigiano J, Gingras AC, Sonenberg N, Burley SK. Cocrystal structure of the messenger RNA 5’ cap-binding protein (eIF4E) bound to 7-methyl-GDP. Cell. 1997;89:951–61.CrossRefPubMedGoogle Scholar
  98. 98.
    Matsuo H, Li H, McGuire AM, Fletcher CM, Gingras AC, Sonenberg N, Wagner G. Structure of translation factor eIF4E bound to m7GDP and interaction with 4E-binding protein. Nature Structural Biology. 1997;4:717–24.CrossRefPubMedGoogle Scholar
  99. 99.
    Osborne MJ, Volpon L, Kornblatt JA, Culjkovic-Kraljacic B, Baguet A, Borden KL. eIF4E3 acts as a tumor suppressor by utilizing an atypical mode of methyl-7-guanosine cap recognition. Proc Natl Acad Sci USA. 2013;110:3877–82.CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Li L, Wang CC. Identification in the ancient protist Giardia lamblia of two eukaryotic translation initiation factor 4E homologues with distinctive functions. Eukaryot Cell. 2005;4:948–59.CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Jankowska-Anyszka M, Lamphear BJ, Aamodt EJ, Harrington T, Darzynkiewicz E, Stolarski R, Rhoads RE. Multiple isoforms of eukaryotic protein synthesis initiation factor 4E in Caenorhabditis elegans can distinguish between mono- and trimethylated mRNA cap structures. J Biol Chem. 1998;273:10538–42.CrossRefPubMedGoogle Scholar
  102. 102.
    Keiper BD, Lamphear BJ, Deshpande AM, Jankowska-Anyszka M, Aamodt EJ, Blumenthal T, Rhoads RE. Functional characterization of five eIF4E isoforms in Caenorhabditis elegans. J Biol Chem. 2000;275:10590–6.CrossRefPubMedGoogle Scholar
  103. 103.
    Standart N, Minshall N. Translational control in early development: CPEB, P-bodies and germinal granules. Biochem Soc Trans. 2008;36:671–6.CrossRefPubMedGoogle Scholar
  104. 104.
    Hernández G, Gandin V, Han H, Ferreira T, Sonenberg N, Lasko P. Translational control by Drosophila eIF4E-3 is essential for cell differentiation during spermiogenesis. Development. 2012;139:3211–20.CrossRefPubMedPubMedCentralGoogle Scholar
  105. 105.
    Hernández G, Altmann M, Sierra JM, Urlaub H, Corral RD, Schwartz P, Rivera-Pomar R. Functional analysis of seven genes encoding eight translation initiation factor 4E (eIF4E) isoforms in Drosophila. Mech Dev. 2005;122:529–43.CrossRefPubMedGoogle Scholar
  106. 106.
    Rom E, Kim HC, Gingras AC, Marcotrigiano J, Favre D, Olsen H, Burley SK, Sonenberg N. Cloning and characterization of 4E-HP, a novel mammalian eIF4E-related cap-binding protein. J Biol Chem. 1998;273:13104–9.CrossRefPubMedGoogle Scholar
  107. 107.
    Ruud KA, Kuhlow C, Goss DJ, Browning KS. Identification and characterization of a novel cap-binding protein from Arabidopsis thaliana. J Biol Chem. 1998;273:10325–30.CrossRefPubMedGoogle Scholar
  108. 108.
    Lasko P. The Drosophila melanogaster genome: translational factors and RNA binding proteins. J Cell Biol. 2000;150:F51–6.CrossRefPubMedGoogle Scholar
  109. 109.
    Gingras AC, Raught B, Sonenberg N. eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation. Annu Rev Biochem. 1999;68:913–63.CrossRefPubMedGoogle Scholar
  110. 110.
    Teleman AA, Chen YW, Cohen SM. 4E-BP functions as a metabolic brake used under stress conditions but not during norml growth. Genes Dev. 2005;19:1844–8.CrossRefPubMedPubMedCentralGoogle Scholar
  111. 111.
    Tettweiler G, Miron M, Jenkins M, Sonenberg N, Lasko P. Starvation and oxidative stress resistance in Drosophila are mediated through the eIF4E-binding protein, d4E-BP. Genes Dev. 2005;19:1840–3.CrossRefPubMedPubMedCentralGoogle Scholar
  112. 112.
    Peter D, Igreja C, Weber R, Wohlbold L, Weiler C, Ebertsch L, Weichenrieder O, Izaurralde E. Molecular architecture of 4E-BP translational inhibitors bound to eIF4E. Mol Cell. 2015;57:1074–87.CrossRefPubMedGoogle Scholar
  113. 113.
    Peter D, Weber R, Kone C, Chung MY, Ebertsch L, Truffault V, Weichenrieder O, Igreja C, Izaurralde E. Mextli proteins use both canonical bipartite and novel tripartite binding modes to form eIF4E complexes that display differential sensitivity to 4E-BP regulation. Genes & Dev. 2015;29:1835–49.CrossRefGoogle Scholar
  114. 114.
    Igreja C, Peter D, Weiler C, Izaurralde E. 4E-BPs require non-canonical 4E-binding motifs and a lateral surface of eIF4E to repress translation. Nature Commun. 2014;5:4790.CrossRefGoogle Scholar
  115. 115.
    Lukhele S, Bah A. H. L, Sonenberg N, Forman-Kay JD. Interaction of the eukaryotic initiation factor 4E with 4E-BP2 at a dynamic bipartite interface. Structure. 2013;21:2186–96.CrossRefPubMedGoogle Scholar
  116. 116.
    Paku KS, Umenaga Y, Usui T, Fukuyo A, Mizuno A, In Y, Ishida T, Tomoo K. A conserved motif within the flexible C-terminus of the translational regulator 4E-BP is required for tight binding to the mRNA cap-binding protein eIF4E. Biochem J. 2012;441:237–45.CrossRefPubMedGoogle Scholar
  117. 117.
    Gingras AC, Kennedy SG, O’Leary MA, Sonenberg N, Hay N. 4E-BP1, a repressor of mRNA translation, is phosphorylated and inactivated by the Akt(PKB) signaling pathway. Genes Dev. 1998;12:502–13.CrossRefPubMedPubMedCentralGoogle Scholar
  118. 118.
    Gingras AC, Raught B, Gygi SP, Niedzwiecka A, Miron M, Burley SK, Polakiewicz RD, Wyslouch-Cieszynska A, Aebersold R, Sonenberg N. Hierarchical phosphorylation of the translation inhibitor 4E-BP1. Genes Dev. 2001;15:2852–64.CrossRefPubMedPubMedCentralGoogle Scholar
  119. 119.
    Cavalier-Smith T. The phagotrophic origin of eukaryotes and phylogenetic classification of Protozoa. Int J Syst Evol Microbiol. 2002;52:297–354.CrossRefPubMedGoogle Scholar
  120. 120.
    He D, Fiz-Palacios O, Fu CJ, Fehling J, Tsai CC, Baldauf SL. An alternative root for the eukaryote tree of life. Curr Biol. 2014;24:465–70.CrossRefPubMedGoogle Scholar
  121. 121.
    Cavalier-Smith T, Chao EE, Snell EA, Berney C, Fiore-Donno AM, Lewis R. Multigene eukaryote phylogeny reveals the likely protozoan ancestors of opisthokonts (animals, fungi, choanozoans) and Amoebozoa. Mol Phylogenet Evol. 2014;81:71–85.CrossRefPubMedGoogle Scholar
  122. 122.
    Topisirovic I, Borden KL. Homeodomain proteins and eukaryotic translation initiation factor 4E (eIF4E): an unexpected relationship. Histol Histopathol. 2005;20:1275–84.PubMedGoogle Scholar
  123. 123.
    Jacob F. Evolution and Tinkering. Science. 1977;196:1161–6.CrossRefPubMedGoogle Scholar
  124. 124.
    Cho PF, Poulin F, Cho-Park YA, Cho-Park IB, Chicoine JD, Lasko P, Sonenberg N. A new paradigm for translational control: inhibition via 5’-3’ mRNA tethering by Bicoid and the eIF4E cognate 4E-HP. Cell. 2005;121:411–23.CrossRefPubMedGoogle Scholar
  125. 125.
    Garcia-Fernandez J. The genesis and evolution of homeobox gene clusters. Nat Rev Genet. 2005;6:881–92.CrossRefPubMedGoogle Scholar
  126. 126.
    McGregor AP. How to get ahead: the origin, evolution and function of bicoid. BioEssays. 2005;27:904–13.CrossRefPubMedGoogle Scholar
  127. 127.
    Rosenberg MI, Lynch JA, Desplan C. Heads and tails: evolution of antero-posterior patterning in insects. Biochim Biophys Acta. 2009;1789:333–42.CrossRefPubMedGoogle Scholar
  128. 128.
    Stauber M, Jäckle H, Schmidt-Ott U. The anterior determinant bicoid of Drosophila is a derived Hox class 3 gene. Proc Natl Acad Sci USA. 1999;96:3786–9.CrossRefPubMedPubMedCentralGoogle Scholar
  129. 129.
    Olesnicky EC, Brent AE, Tonnes L, Walker M, Pultz MA, Leaf D, Desplan C. A caudal mRNA gradient controls posterior development in the wasp Nasonia. Development. 2006;133:3973–82.CrossRefPubMedGoogle Scholar
  130. 130.
    Stauber M, Prell A, Schmidt-Ott U. A single Hox3 gene with composite bicoid and zerknüllt expression characteristics in non-Cyclorrhaphan flies. Proc Natl Acad Sci USA. 2002;99:274–9.CrossRefPubMedPubMedCentralGoogle Scholar
  131. 131.
    Freire ER, Dhalia R, Moura DM, Lima TD, Lima RP, Reis CR, Hughes K, Figueiredo RC, Standart N, Carrington M, de Melo NOP. The four trypanosomatid eIF4E homologues fall into two separate groups, with distinct features in primary sequence and biological properties. Mol Biochem Parasitol. 2011;176:25–36.CrossRefPubMedGoogle Scholar
  132. 132.
    Lipovich L, Hughes AL, King MC, Abkowitz JL, Quigley JG. Genomic structure and evolutionary context of the human feline leukemia virus subgroup C receptor (hFLVCR) gene: evidence for block duplications and de novo gene formation within duplicons of the hFLVCR locus. Gene. 2002;286:203–13.CrossRefPubMedGoogle Scholar
  133. 133.
    Sekiyama N, Arthanari H, Papadopoulos E, Rodriguez-Mias RA, Wagner G, Leger-Abraham M. Molecular mechanism of the dual activity of 4EGI-1: Dissociating eIF4G from eIF4E but stabilizing the binding of unphosphorylated 4E-BP1. Proc Natl Acad Sci USA. 2015;112:E4036–45.CrossRefPubMedPubMedCentralGoogle Scholar
  134. 134.
    Kinkelin K, Veith K, Grunwald M, Bono F. Crystal structure of a minimal eIF4E-Cup complex reveals a general mechanism of eIF4E regulation in translational repression. RNA. 2012;18:1624–34.CrossRefPubMedPubMedCentralGoogle Scholar
  135. 135.
    Nelson MR, Leidal AM, Smibert CA. Drosophila Cup is an eIF4E-binding protein that functions in Smaug-mediated translational repression. EMBO J. 2004;23:150–9.CrossRefPubMedGoogle Scholar
  136. 136.
    Mizuno A, In Y, Fujita Y, Abiko F, Miyagawa H, Kitamura K, Tomoo K, Ishida T. mportance of C-terminal flexible region of 4E-binding protein in binding with eukaryotic initiation factor 4E. FEBS Lett. 2008;582:3439–44.CrossRefPubMedGoogle Scholar
  137. 137.
    Ritter B, Denisov AY, Philie J, Deprez C, Tung EC, Gehring K, McPherson PS. Two WXXF-based motifs in NECAPs define the specificity of accessory protein binding to AP-1 and AP-2. EMBO J. 2004;23:3701–10.CrossRefPubMedPubMedCentralGoogle Scholar
  138. 138.
    Gosselin P, Oulhen N, Jam M, Ronzca J, Cormier P, Czjzek M, Cosson B. The translational repressor 4E-BP called to order by eIF4E: new structural insights by SAXS. Nucleic Acid Res. 2011;39:3496–503.CrossRefPubMedGoogle Scholar
  139. 139.
    Fletcher CM, Wagner G. The interaction of eIF4E with 4E-BP1 is an induced fit to a completely disordered protein. Protein Sci. 1998;7:1639–42.CrossRefPubMedPubMedCentralGoogle Scholar
  140. 140.
    Fletcher CM, McGuire AM, Gingras AC, Li H, Matsuo H, Sonenberg N, Wagner G. 4E binding proteins inhibit the translation factor eIF4E without folded structure. Biochemistry. 1998;37:9–15.CrossRefPubMedGoogle Scholar
  141. 141.
    Tompa P. Intrinsically disordered proteins: a 10-year recap. Trends Biochem Sci. 2012;37:509–16.CrossRefPubMedGoogle Scholar
  142. 142.
    Dyson HJ, Wright PE. Intrinsically unstructured proteins and their functions. Nat Rev Mol Cell Biol. 2005;6:197–208.CrossRefPubMedGoogle Scholar
  143. 143.
    Stein A, Pache RA, Bernado P, Pons M, Aloy P. Dynamic interactions of proteins in complex networks: a more structured view. FEBS J. 2009;276:5390–405.CrossRefPubMedGoogle Scholar
  144. 144.
    Papadopoulos E, Jenni S, Kabha E, Takrouri KJ, Yi T, Salvi N, Luna RE, Gavathiotis E, Mahalingam P, Arthanari H, Rodriguez-Mias R, Yefidoff-Freedman R, Aktas BH, Chorev M, Halperin JA, Wagner G. Structure of the eukaryotic translation initiation factor eIF4E in complex with 4EGI-1 reveals an allosteric mechanism for dissociating eIF4G. Proc Natl Acad Sci USA. 2014;111:E3187–95.CrossRefPubMedPubMedCentralGoogle Scholar
  145. 145.
    Moerke NJ, Aktas H, Chen H, Cantel S, Reibarkh MY, Fahmy A, Gross JD, Degterev A, Yuan J, Chorev MH. J.A., Wagner G. Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Cell. 2007;128:257–67.CrossRefPubMedGoogle Scholar
  146. 146.
    Cencic R, Desforges M, Hall DR, Kozakov D, Du Y, Min J, Dingledine R, Fu H, Vajda S, Talbot PJ, Pelletier J. Blocking eIF4E-eIF4G interaction as a strategy to impair coronavirus replication. J Virol. 2011;85:6381–9.CrossRefPubMedPubMedCentralGoogle Scholar
  147. 147.
    Cencic R, Hall DR, Robert F, Du Y, Min J, Li L, Qui M, Lewis I, Kurtkaya S, Dingledine R, Fu H, Kozakov D, Vajda S, Pelletier J. Reversing chemoresistance by small molecule inhibition of the translation initiation complex eIF4F. Proc Natl Acad Sci USA. 2011;108:1046–51.CrossRefPubMedGoogle Scholar
  148. 148.
    Lee T, Pelletier J. Eukaryotic initiation factor 4F: a vulnerability of tumor cells. Future Med Chem. 2012;4:19–31.CrossRefPubMedGoogle Scholar
  149. 149.
    Gross JD, Moerke NJ, von der Haar T, Lugovskoy AA, Sachs AB, McCarthy JE, Wagner G. Ribosome loading onto the mRNA cap is driven by conformational coupling between eIF4G and eIF4E. Cell. 2003;115:739–50.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Greco Hernández
    • 1
    Email author
  • Kathleen M. Gillespie
    • 2
  • Tsvetan R. Bachvaroff
    • 2
  • Rosemary Jagus
    • 2
  • Cátia Igreja
    • 3
  • Daniel Peter
    • 3
  • Manuel Bulfoni
    • 4
  • Bertrand Cosson
    • 4
  1. 1.Division of Basic ResearchNational Institute of Cancer (INCan)Mexico CityMexico
  2. 2.Institute of Marine and Environmental TechnologyUniversity of Maryland Center for Environmental ScienceBaltimoreUSA
  3. 3.Department of BiochemistryMax Planck Institute for Developmental BiologyTübingenGermany
  4. 4.Université Paris DiderotParisFrance

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