Biochemical and Structural Insights into the Eukaryotic Translation Initiation Factor eIF4E

Author(s): Laurent Volpon, Michael J. Osborne, Katherine L.B. Borden*

Journal Name: Current Protein & Peptide Science

Volume 20 , Issue 6 , 2019

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Graphical Abstract:


A major question in cell and cancer biology is concerned with understanding the flow of information from gene to protein. Indeed, many studies indicate that the proteome can be decoupled from the transcriptome. A major source of this decoupling is post-transcriptional regulation. The eukaryotic translation initiation factor eIF4E serves as an excellent example of a protein that can modulate the proteome at the post-transcriptional level. eIF4E is elevated in many cancers thus highlighting the relevance of this mode of control to biology. In this review, we provide a brief overview of various functions of eIF4E in RNA metabolism e.g. in nuclear-cytoplasmic RNA export, translation, RNA stability and/or sequestration. We focus on the modalities of eIF4E regulation at the biochemical and particularly structural level. In this instance, we describe not only the importance for the m7Gcap eIF4E interaction but also of recently discovered non-traditional RNA-eIF4E interactions as well as cap-independent activities of eIF4E. Further, we describe several distinct structural modalities used by the cell and some viruses to regulate or co-opt eIF4E, substantially extending the types of proteins that can regulate eIF4E from the traditional eIF4E-binding proteins (e.g. 4E-BP1 and eIF4G). Finally, we provide an overview of the results of targeting eIF4E activity in the clinic.

Keywords: RNA stability; clinical trials, eIF4E, eIF4E regulators, mRNA export, ribavirin, translation initiation factor.

Lu, X.; de la Pena, L.; Barker, C.; Camphausen, K.; Tofilon, P.J. Radiation-induced changes in gene expression involve recruitment of existing messenger RNAs to and away from polysomes. Cancer Res., 2006, 66, 1052-1061.
Vogel, C.; Abreu Rde, S.; Ko, D.; Le, S.Y.; Shapiro, B.A.; Burns, S.C.; Sandhu, D.; Boutz, D.R.; Marcotte, E.M.; Penalva, L.O. Sequence signatures and mRNA concentration can explain two-thirds of protein abundance variation in a human cell line. Mol. Syst. Biol., 2010, 6, 400.
Zhang, B.; Wang, J.; Wang, X.; Zhu, J.; Liu, Q.; Shi, Z.; Chambers, M.C.; Zimmerman, L.J.; Shaddox, K.F.; Kim, S.; Davies, S.R.; Wang, S.; Wang, P.; Kinsinger, C.R.; Rivers, R.C.; Rodriguez, H.; Townsend, R.R.; Ellis, M.J.; Carr, S.A.; Tabb, D.L.; Coffey, R.J.; Slebos, R.J.; Liebler, D.C. NCI CPTAC. Proteogenomic characterization of human colon and rectal cancer. Nature, 2014, 513, 382-387.
Keene, J.D. RNA regulons: Coordination of post-transcriptional events. Nat. Rev. Genet., 2007, 8, 533-543.
Keene, J.D. Minireview: Global regulation and dynamics of ribonucleic acid. Endocrinology, 2010, 151, 1391-1397.
Keene, J.D.; Lager, P.J. Post-transcriptional operons and regulons co-ordinating gene expression. Chromosome Res., 2005, 13, 327-337.
Keene, J.D.; Tenenbaum, S.A. Eukaryotic mRNPs may represent posttranscriptional operons. Mol. Cell, 2002, 9, 1161-1167.
Carroll, M.; Borden, K.L. The oncogene eIF4E: Using biochemical insights to target cancer. J. Interferon Cytokine Res., 2013, 33, 227-238.
Borden, K.L.; Culjkovic-Kraljacic, B. Ribavirin as an anti-cancer therapy: Acute myeloid leukemia and beyond? Leuk. Lymphoma, 2010, 51, 1805-1815.
Proud, C.G. Mnks, eIF4E phosphorylation and cancer. Biochim. Biophys. Acta, 2015, 1849, 766-773.
Topisirovic, I.; Ruiz-Gutierrez, M.; Borden, K.L. Phosphorylation of the eukaryotic translation initiation factor eIF4E contributes to its transformation and mRNA transport activities. Cancer Res., 2004, 64, 8639-8642.
Wendel, H.G.; Silva, R.L.; Malina, A.; Mills, J.R.; Zhu, H.; Ueda, T.; Watanabe-Fukunaga, R.; Fukunaga, R.; Teruya-Feldstein, J.; Pelletier, J.; Lowe, S.W. Dissecting eIF4E action in tumorigenesis. Genes Dev., 2007, 21, 3232-3237.
Ruggero, D.; Montanaro, L.; Ma, L.; Xu, W.; Londei, P.; Cordon-Cardo, C.; Pandolfi, P.P. The translation factor eIF-4E promotes tumor formation and cooperates with c-Myc in lymphomagenesis. Nat. Med., 2004, 10, 484-486.
Truitt, M.L.; Conn, C.S.; Shi, Z.; Pang, X.; Tokuyasu, T.; Coady, A.M.; Seo, Y.; Barna, M.; Ruggero, D. Differential requirements for eIF4E dose in normal development and cancer. Cell, 2015, 162, 59-71.
Filipowicz, W.; Furuichi, Y.; Sierra, J.M.; Muthukrishnan, S.; Shatkin, A.J.; Ochoa, S. A protein binding the methylated 5′-terminal sequence, m7GpppN, of eukaryotic messenger RNA. Proc. Natl. Acad. Sci. USA, 1976, 73, 1559-1563.
Sonenberg, N. Gingras, A.C. The mRNA 5′ cap-binding protein eIF4E and control of cell growth. Curr. Opin. Cell Biol., 1998, 10, 268-275.
Clemens, M.J.; Bommer, U.A. Translational control: The cancer connection. Int. J. Biochem. Cell Biol., 1999, 31, 1-23.
De Benedetti, A.; Graff, J.R. eIF-4E expression and its role in malignancies and metastases. Oncogene, 2004, 23, 3189-3199.
Culjkovic, B.; Tan, K.; Orolicki, S.; Amri, A.; Meloche, S.; Borden, K.L. The eIF4E RNA regulon promotes the Akt signaling pathway. J. Cell Biol., 2008, 181, 51-63.
Culjkovic, B.; Topisirovic, I.; Skrabanek, L.; Ruiz-Gutierrez, M.; Borden, K.L. eIF4E promotes nuclear export of cyclin D1 mRNAs via an element in the 3'UTR. J. Cell Biol., 2005, 169, 245-256.
Culjkovic, B.; Topisirovic, I.; Skrabanek, L.; Ruiz-Gutierrez, M.; Borden, K.L. eIF4E is a central node of an RNA regulon that governs cellular proliferation. J. Cell Biol., 2006, 175, 415-426.
Merrick, W.C. eIF4F: A retrospective. J. Biol. Chem., 2015, 290, 24091-24099.
Malka-Mahieu, H.; Newman, M.; Desaubry, L.; Robert, C.; Vagner, S. Molecular pathways: The eIF4F translation initiation complex-new opportunities for cancer treatment. Clin. Cancer Res., 2017, 23, 21-25.
Roux, P.P.; Topisirovic, I. Signaling pathways involved in the regulation of mRNA translation. Mol. Cell. Biol., 2018, 38(12), e00070-e18.
Eliseev, B.; Yeramala, L.; Leitner, A.; Karuppasamy, M.; Raimondeau, E.; Huard, K.; Alkalaeva, E.; Aebersold, R.; Schaffitzel, C. Structure of a human cap-dependent 48S translation pre-initiation complex. Nucleic Acids Res., 2018, 46, 2678-2689.
Lejbkowicz, F.; Goyer, C.; Darveau, A.; Neron, S.; Lemieux, R.; Sonenberg, N. A fraction of the mRNA 5′ cap-binding protein, eukaryotic initiation factor 4E, localizes to the nucleus. Proc. Natl. Acad. Sci. USA, 1992, 89, 9612-9616.
Rousseau, D.; Kaspar, R.; Rosenwald, I.; Gehrke, L.; Sonenberg, N. Translation initiation of ornithine decarboxylase and nucleocytoplasmic transport of cyclin D1 mRNA are increased in cells overexpressing eukaryotic initiation factor 4E. Proc. Natl. Acad. Sci. USA, 1996, 93, 1065-1070.
Topisirovic, I.; Siddiqui, N.; Lapointe, V.L.; Trost, M.; Thibault, P.; Bangeranye, C.; Piñol-Roma, S.; Borden, K.L. Molecular dissection of the eukaryotic initiation factor 4E (eIF4E) export-competent RNP. EMBO J., 2009, 28, 1087-1098.
Volpon, L.; Culjkovic-Kraljacic, B.; Sohn, H.S.; Blanchet-Cohen, A.; Osborne, M.J.; Borden, K.L.B. A biochemical framework for eIF4E-dependent mRNA export and nuclear recycling of the export machinery. RNA, 2017, 23, 927-937.
Culjkovic-Kraljacic, B.; Baguet, A.; Volpon, L.; Amri, A.; Borden, K.L. The oncogene eIF4E reprograms the nuclear pore complex to promote mRNA export and oncogenic transformation. Cell Reports, 2012, 2, 207-215.
Culjkovic-Kraljacic, B.; Baguet, A.; Volpon, L.; Amri, A.; Borden, K.L.B. The oncogene eIF4E reprograms the nuclear pore complext to promote mRNA export and oncogenic transformation. Cell Reports, 2012, 2, 207-215.
Culjkovic-Kraljacic, B.; Fernando, T.M.; Marullo, R.; Calvo-Vidal, N.; Verma, A.; Yang, S.; Tabbò, F.; Gaudiano, M.; Zahreddine, H.; Goldstein, R.L.; Patel, J.; Taldone, T.; Chiosis, G.; Ladetto, M.; Ghione, P.; Machiorlatti, R.; Elemento, O.; Inghirami, G.; Melnick, A.; Borden, K.L.; Cerchietti, L. Combinatorial targeting of nuclear export and translation of RNA inhibits aggressive B-cell lymphomas. Blood, 2016, 127, 858-868.
Zahreddine, H.A.; Culjkovic-Kraljacic, B.; Emond, A.; Pettersson, F.; Midura, R.; Lauer, M.; Del Rincon, S.; Cali, V.; Assouline, S.; Miller, W.H.; Hascall, V.; Borden, K.L. The eukaryotic translation initiation factor eIF4E harnesses hyaluronan production to drive its malignant activity. eLife, 2017, 6, e29830.
Andrei, M.A.; Ingelfinger, D.; Heintzmann, R.; Achsel, T.; Rivera-Pomar, R.; Luhrmann, R. A role for eIF4E and eIF4E-transporter in targeting mRNPs to mammalian processing bodies. RNA, 2005, 11, 717-727.
Ferraiuolo, M.A.; Basak, S.; Dostie, J.; Murray, E.L.; Schoenberg, D.R.; Sonenberg, N. A role for the eIF4E-binding protein 4E-T in P-body formation and mRNA decay. J. Cell Biol., 2005, 170, 913-924.
Cargnello, M.; Tcherkezian, J.; Dorn, J.F.; Huttlin, E.L.; Maddox, P.S.; Gygi, S.P.; Roux, P.P. Phosphorylation of the eukaryotic translation initiation factor 4E-transporter (4E-T) by c-Jun N-terminal kinase promotes stress-dependent P-body assembly. Mol. Cell. Biol., 2012, 32, 4572-4584.
Mikhailova, T.; Shuvalova, E.; Ivanov, A.; Susorov, D.; Shuvalov, A.; Kolosov, P.M.; Alkalaeva, E. RNA helicase DDX19 stabilizes ribosomal elongation and termination complexes. Nucleic Acids Res., 2017, 45, 1307-1318.
Decker, C.J.; Parker, R. P-bodies and stress granules: Possible roles in the control of translation and mRNA degradation. Cold Spring Harb. Perspect. Biol., 2012, 4, a012286.
Borden, K.L. The eukaryotic translation initiation factor eIF4E wears a “cap” for many occasions. Translation (Austin), 2016, 4, e1220899.
Marcotrigiano, J.; Gingras, A.C.; Sonenberg, N.; Burley, S.K. Cocrystal structure of the messenger RNA 5′ cap-binding protein (eIF4E) bound to 7-methyl-GDP. Cell, 1997, 89, 951-961.
Matsuo, H.; Li, H.; McGuire, A.M.; Fletcher, C.M.; Gingras, A.C.; Sonenberg, N.; Wagner, G. Structure of translation factor eIF4E bound to m7GDP and interaction with 4E-binding protein. Nat. Struct. Biol., 1997, 4, 717-724.
Volpon, L.; Osborne, M.J.; Topisirovic, I.; Siddiqui, N.; Borden, K.L. Cap-free structure of eIF4E suggests a basis for conformational regulation by its ligands. EMBO J., 2006, 25, 5138-5149.
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. Biophysical studies of eIF4E cap-binding protein: Recognition of mRNA 5′ cap structure and synthetic fragments of eIF4G and 4E-BP1 proteins. J. Mol. Biol., 2002, 319, 615-635.
Brown, C.J.; McNae, I.; Fischer, P.M.; Walkinshaw, M.D. Crystallographic and mass spectrometric characterisation of eIF4E with N7-alkylated cap derivatives. J. Mol. Biol., 2007, 372, 7-15.
Marcotrigiano, J.; Gingras, A.C.; Sonenberg, N.; Burley, S.K. Cap-dependent translation initiation in eukaryotes is regulated by a molecular mimic of eIF4G. Mol. Cell, 1999, 3, 707-716.
Siddiqui, N.; Tempel, W.; Nedyalkova, L.; Volpon, L.; Wernimont, A.K.; Osborne, M.J.; Park, H.W.; Borden, K.L. Structural insights into the allosteric effects of 4EBP1 on the eukaryotic translation initiation factor eIF4E. J. Mol. Biol., 2012, 415, 781-792.
Ptushkina, M.; von der Haar, T.; Karim, M.M.; Hughes, J.M.; McCarthy, J.E. Repressor binding to a dorsal regulatory site traps human eIF4E in a high cap-affinity state. EMBO J., 1999, 18, 4068-4075.
Lukhele, S.; Bah, A.; Lin, H.; Sonenberg, N.; Forman-Kay, J.D. Interaction of the eukaryotic initiation factor 4E with 4E-BP2 at a dynamic bipartite interface. Structure, 2013, 21, 2186-2196.
Salvi, N.; Papadopoulos, E.; Blackledge, M.; Wagner, G. The role of dynamics and allostery in the inhibition of the eIF4E/eIF4G translation initiation factor complex. Angew. Chem. Int. Ed. Engl., 2016, 55, 7176-7179.
von Der Haar, T.; Ball, P.D.; McCarthy, J.E. Stabilization of eukaryotic initiation factor 4E binding to the mRNA 5′-Cap by domains of eIF4G. J. Biol. Chem., 2000, 275, 30551-30555.
Friedland, D.E.; Wooten, W.N.; LaVoy, J.E.; Hagedorn, C.H.; Goss, D.J. A mutant of eukaryotic protein synthesis initiation factor eIF4E(K119A) has an increased binding affinity for both m7G cap analogues and eIF4G peptides. Biochemistry, 2005, 44, 4546-4550.
Kentsis, A.; Dwyer, E.C.; Perez, J.M.; Sharma, M.; Chen, A.; Pan, Z.Q.; Borden, K.L. 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, 609-623.
Volpon, L.; Osborne, M.J.; Capul, A.A.; de la Torre, J.C.; Borden, K.L. Structural characterization of the Z RING-eIF4E complex reveals a distinct mode of control for eIF4E. Proc. Natl. Acad. Sci. USA, 2010, 107, 5441-5446.
Kentsis, A.; Gordon, R.E.; Borden, K.L. Control of biochemical reactions through supramolecular RING domain self-assembly. Proc. Natl. Acad. Sci. USA, 2002, 99, 15404-15409.
Modrak-Wojcik, A.; Gorka, M.; Niedzwiecka, K.; Zdanowski, K.; Zuberek, J.; Niedzwiecka, A.; Stolarski, R. Eukaryotic translation initiation is controlled by cooperativity effects within ternary complexes of 4E-BP1, eIF4E, and the mRNA 5′ cap. FEBS Lett., 2013, 587, 3928-3934.
Joshi, B.; Cameron, A.; Jagus, R. Characterization of mammalian eIF4E-family members. Eur. J. Biochem., 2004, 271, 2189-2203.
Rosettani, P.; Knapp, S.; Vismara, M.G.; Rusconi, L.; Cameron, A.D. Structures of the human eIF4E homologous protein, h4EHP, in its m7GTP-bound and unliganded forms. J. Mol. Biol., 2007, 368, 691-705.
Osborne, M.J.; Volpon, L.; Kornblatt, J.A.; Culjkovic-Kraljacic, B.; Baguet, A.; Borden, K.L. eIF4E3 acts as a tumor suppressor by utilizing an atypical mode of methyl-7-guanosine cap recognition. Proc. Natl. Acad. Sci. USA, 2013, 110, 3877-3882.
Amaya Ramirez, C.C.; Hubbe, P.; Mandel, N.; Bethune, J. 4EHP-independent repression of endogenous mRNAs by the RNA-binding protein GIGYF2. Nucleic Acids Res., 2018, 46, 5792-5808.
Landon, A.L.; Muniandy, P.A.; Shetty, A.C.; Lehrmann, E.; Volpon, L.; Houng, S.; Zhang, Y.; Dai, B.; Peroutka, R.; Mazan-Mamczarz, K.; Steinhardt, J.; Mahurkar, A.; Becker, K.G.; Borden, K.L.; Gartenhaus, R.B. MNKs act as a regulatory switch for eIF4E1 and eIF4E3 driven mRNA translation in DLBCL. Nat. Commun., 2014, 5, 5413.
Melanson, G.; Timpano, S.; Uniacke, J. The eIF4E2-directed hypoxic cap-dependent translation machinery reveals novel therapeutic potential for cancer treatment. Oxid. Med. Cell. Longev., 2017, 2017, 6098107.
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, 1074-1087.
Gruner, S.; Weber, R.; Peter, D.; Chung, M.Y.; Igreja, C.; Valkov, E.; Izaurralde, E. Structural motifs in eIF4G and 4E-BPs modulate their binding to eIF4E to regulate translation initiation in yeast. Nucleic Acids Res., 2018, 46, 6893-6908.
Arndt, N.; Ross-Kaschitza, D.; Kojukhov, A.; Komar, A.A.; Altmann, M. Properties of the ternary complex formed by yeast eIF4E, p20 and mRNA. Sci. Rep., 2018, 8, 6707.
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 gamma and the translational repressors 4E-binding proteins. Mol. Cell. Biol., 1995, 15, 4990-4997.
Macdonald, P.M. Translational repression by Bicoid: Competition for the cap. Cell, 2005, 121, 321-322.
Nedelec, 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, 10815-10820.
Topisirovic, I.; Kentsis, A.; Perez, J.M.; Guzman, M.L.; Jordan, C.T.; Borden, K.L. Eukaryotic translation initiation factor 4E activity is modulated by HOXA9 at multiple levels. Mol. Cell. Biol., 2005, 25, 1100-1112.
Niessing, D.; Blanke, S.; Jackle, H. Bicoid associates with the 5′-cap-bound complex of caudal mRNA and represses translation. Genes Dev., 2002, 16, 2576-2582.
Gruner, S.; Peter, D.; Weber, R.; Wohlbold, L.; Chung, M.Y.; Weichenrieder, O.; Valkov, E.; Igreja, C.; Izaurralde, E. The structures of eIF4E-eIF4G complexes reveal an extended interface to regulate translation initiation. Mol. Cell, 2016, 64, 467-479.
Tan, N.G.; Ardley, H.C.; Scott, G.B.; Rose, S.A.; Markham, A.F.; Robinson, P.A. Human homologue of ariadne promotes the ubiquitylation of translation initiation factor 4E homologous protein, 4EHP. FEBS Lett., 2003, 554, 501-504.
Volpon, L.; Culjkovic-Kraljacic, B.; Osborne, M.J.; Ramteke, A.; Sun, Q.; Niesman, A.; Chook, Y.M.; Borden, K.L. Importin 8 mediates m7G cap-sensitive nuclear import of the eukaryotic translation initiation factor eIF4E. Proc. Natl. Acad. Sci. USA, 2016, 113, 5263-5268.
Chook, Y.M.; Blobel, G. Structure of the nuclear transport complex karyopherin-beta2-Ran x GppNHp. Nature, 1999, 399, 230-237.
Lightowlers, R.N.; Chrzanowska-Lightowlers, Z.M. Human pentatricopeptide proteins: only a few and what do they do? RNA Biol., 2013, 10, 1433-1438.
Truniger, V.; Aranda, M.A. Recessive resistance to plant viruses. Adv. Virus Res., 2009, 75, 119-159.
Coutinho de Oliveira, L.; Volpon, L.; Osborne, M.J.; Borden, K.L.B. Chemical shift assignment of the viral protein genome-linked (VPg) from potato virus Y. Biomol. NMR Assign., 2018. [Epub ahead of print].
Kentsis, A.; Volpon, L.; Topisirovic, I.; Soll, C.E.; Culjkovic, B.; Shao, L.; Borden, K.L. Further evidence that ribavirin interacts with eIF4E. RNA, 2005, 11, 1762-1766.
Kentsis, A.; Topisirovic, I.; Culjkovic, B.; Shao, L.; Borden, K.L. Ribavirin suppresses eIF4E-mediated oncogenic transformation by physical mimicry of the 7-methyl guanosine mRNA cap. Proc. Natl. Acad. Sci. USA, 2004, 101, 18105-18110.
Volpon, L.; Osborne, M.J.; Zahreddine, H.; Romeo, A.A.; Borden, K.L. Conformational changes induced in the eukaryotic translation initiation factor eIF4E by a clinically relevant inhibitor, ribavirin triphosphate. Biochem. Biophys. Res. Commun., 2013, 434, 614-619.
Zahreddine, H.A.; Culjkovic-Kraljacic, B.; Assouline, S.; Gendron, P.; Romeo, A.A.; Morris, S.J.; Cormack, G.; Jaquith, J.B.; Cerchietti, L.; Cocolakis, E.; Amri, A.; Bergeron, J.; Leber, B.; Becker, M.W.; Pei, S.; Jordan, C.T.; Miller, W.H.; Borden, K.L. The sonic hedgehog factor GLI1 imparts drug resistance through inducible glucuronidation. Nature, 2014, 511, 90-93.
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. Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Cell, 2007, 128, 257-267.
Papadopoulos, E.; Jenni, S.; Kabha, E.; Takrouri, K.J.; Yi, T.; Salvi, N.; Luna, R.E.; Gavathiotis, E.; Mahalingam, P.; Arthanari, H.; Rodriguez-Mias, R.; Yefidoff-Freedman, R.; Aktas, B.H.; Chorev, M.; Halperin, J.A.; 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-E3195.
Harris, B.R.E.; Wang, D.; Zhang, Y.; Ferrari, M.; Okon, A.; Cleary, M.P.; Wagner, C.R.; Yang, D.Q. Induction of the p53 tumor suppressor in cancer cells through inhibition of cap-dependent translation. Mol. Cell. Biol., 2018, 38(10), e00367-e17.
Liu, W.; Jankowska-Anyszka, M.; Piecyk, K.; Dickson, L.; Wallace, A.; Niedzwiecka, A.; Stepinski, J.; Stolarski, R.; Darzynkiewicz, E.; Kieft, J.; Zhao, R.; Jones, D.N.; Davis, R.E. Structural basis for nematode eIF4E binding an m(2,2,7)G-Cap and its implications for translation initiation. Nucleic Acids Res., 2011, 39, 8820-8832.
Wallace, A.; Filbin, M.E.; Veo, B.; McFarland, C.; Stepinski, J.; Jankowska-Anyszka, M.; Darzynkiewicz, E.; Davis, R.E. The nematode eukaryotic translation initiation factor 4E/G complex works with a trans-spliced leader stem-loop to enable efficient translation of trimethylguanosine-capped RNAs. Mol. Cell. Biol., 2010, 30, 1958-1970.
Dostie, J.; Lejbkowicz, F.; Sonenberg, N. Nuclear eukaryotic initiation factor 4E (eIF4E) colocalizes with splicing factors in speckles. J. Cell Biol., 2000, 148, 239-247.
Yedavalli, V.S.; Jeang, K.T. Trimethylguanosine capping selectively promotes expression of Rev-dependent HIV-1 RNAs. Proc. Natl. Acad. Sci. USA, 2010, 107, 14787-14792.
Browning, K.S. The plant translational apparatus. Plant Mol. Biol., 1996, 32, 107-144.
Gallie, D.R.; Browning, K.S. eIF4G functionally differs from eIFiso4G in promoting internal initiation, cap-independent translation, and translation of structured mRNAs. J. Biol. Chem., 2001, 276, 36951-36960.
Miras, M.; Miller, W.A.; Truniger, V.; Aranda, M.A. Non-canonical translation in plant RNA viruses. Front. Plant Sci., 2017, 8, 494.
Martin, F.; Barends, S.; Jaeger, S.; Schaeffer, L.; Prongidi-Fix, L.; Eriani, G. Cap-assisted internal initiation of translation of histone H4. Mol. Cell, 2011, 41, 197-209.
Feoktistova, K.; Tuvshintogs, E.; Do, A.; Fraser, C.S. Human eIF4E promotes mRNA restructuring by stimulating eIF4A helicase activity. Proc. Natl. Acad. Sci. USA, 2013, 110, 13339-13344.
Graff, J.R.; Konicek, B.W.; Vincent, T.M.; Lynch, R.L.; Monteith, D.; Weir, S.N.; Schwier, P.; Capen, A.; Goode, R.L.; Dowless, M.S.; Chen, Y.; Zhang, H.; Sissons, S.; Cox, K.; McNulty, A.M.; Parsons, S.H.; Wang, T.; Sams, L.; Geeganage, S.; Douglass, L.E.; Neubauer, B.L.; Dean, N.M.; Blanchard, K.; Shou, J.; Stancato, L.F.; Carter, J.H.; Marcusson, E.G. Therapeutic suppression of translation initiation factor eIF4E expression reduces tumor growth without toxicity. J. Clin. Invest., 2007, 117, 2638-2648.
Topisirovic, I.; Guzman, M.L.; McConnell, M.J.; Licht, J.D.; Culjkovic, B.; Neering, S.J.; Jordan, C.T.; Borden, K.L. Aberrant eukaryotic translation initiation factor 4E-dependent mRNA transport impedes hematopoietic differentiation and contributes to leukemogenesis. Mol. Cell. Biol., 2003, 23, 8992-9002.
Wendel, H.G.; De Stanchina, E.; Fridman, J.S.; Malina, A.; Ray, S.; Kogan, S.; Cordon-Cardo, C.; Pelletier, J.; Lowe, S.W. Survival signalling by Akt and eIF4E in oncogenesis and cancer therapy. Nature, 2004, 428, 332-337.
Assouline, S.; Culjkovic, B.; Cocolakis, E.; Rousseau, C.; Beslu, N.; Amri, A.; Caplan, S.; Leber, B.; Roy, D.C.; Miller, W.H. Jr, Borden, K.L. Molecular targeting of the oncogene eIF4E in acute myeloid leukemia (AML): A proof-of-principle clinical trial with ribavirin. Blood, 2009, 114, 257-260.
Assouline, S.; Culjkovic-Kraljacic, B.; Bergeron, J.; Caplan, S.; Cocolakis, E.; Lambert, C.; Lau, C.J.; Zahreddine, H.A.; Miller, W.H., Jr A phase I trial of ribavirin and low-dose cytarabine for the treatment of relapsed and refractory acute myeloid leukemia with elevated eIF4E. Haematologica, 2015, 100, e7-e9.
Hong, D.S.; Kurzrock, R.; Oh, Y.; Wheler, J.; Naing, A.; Brail, L.; Callies, S.; André, V.; Kadam, S.K.; Nasir, A.; Holzer, T.R.; Meric-Bernstam, F.; Fishman, M.; Simon, G. A phase 1 dose escalation, pharmacokinetic, and pharmacodynamic evaluation of eIF-4E antisense oligonucleotide LY2275796 in patients with advanced cancer. Clin. Cancer Res., 2011, 17, 6582-6591.
Dunn, L.A.; Fury, M.G.; Sherman, E.J.; Ho, A.A.; Katabi, N.; Haque, S.S.; Pfister, D.G. Phase I study of induction chemotherapy with afatinib, ribavirin, and weekly carboplatin and paclitaxel for stage IVA/IVB human papillomavirus-associated oropharyngeal squamous cell cancer. Head Neck, 2018, 40, 233-241.
Kosaka, T.; Maeda, T.; Shinojima, T.; Nagata, H.; Mizuno, R.; Oya, M. A clinical study to evaluate the efficacy and safety of docetaxel with ribavirin in patients with progressive castration resistant prostate cancer who have previously received docetaxel alone. J. Clin. Oncol., 2017, 35, e14010.
Peter, D.; Weber, R.; Sandmeir, F.; Wohlbold, L.; Helms, S.; Bawankar, P.; Valkov, E.; Igreja, C.; Izaurralde, E. GIGYF1/2 proteins use auxiliary sequences to selectively bind to 4EHP and repress target mRNA expression. Genes Dev., 2017, 31, 1147-1161.

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Article Details

Year: 2019
Published on: 10 January, 2019
Page: [525 - 535]
Pages: 11
DOI: 10.2174/1389203720666190110142438
Price: $65

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