Molecular mechanism of the dual activity of 4EGI-1: Dissociating eIF4G from eIF4E but stabilizing the binding of unphosphorylated 4E-BP1

Sekiyama, Naotaka; Arthanari, Haribabu; Papadopoulos, Evangelos; Rodriguez-Mias, Ricard A.; Wagner, Gerhard; Léger-Abraham, Mélissa

doi:10.1073/pnas.1512118112

Title: Molecular mechanism of the dual activity of 4EGI-1: Dissociating eIF4G from eIF4E but stabilizing the binding of unphosphorylated 4E-BP1

Journal Article · Mon Jul 13 00:00:00 EDT 2015 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1512118112· OSTI ID:1208688

Sekiyama, Naotaka ^[1]; Arthanari, Haribabu ^[1]; Papadopoulos, Evangelos ^[1]; Rodriguez-Mias, Ricard A. ^[1]; Wagner, Gerhard ^[1]; Léger-Abraham, Mélissa ^[1]

Harvard Medical School, Boston, MA (United States). Dept. of Biological Chemistry and Molecular Pharmacology

The eIF4E-binding protein (4E-BP) is a phosphorylation-dependent regulator of protein synthesis. The nonphosphorylated or minimally phosphorylated form binds translation initiation factor 4E (eIF4E), preventing binding of eIF4G and the recruitment of the small ribosomal subunit. Signaling events stimulate serial phosphorylation of 4E-BP, primarily by mammalian target of rapamycin complex 1 (mTORC1) at residues T₃₇/T₄₆, followed by T₇₀ and S₆₅. Hyperphosphorylated 4E-BP dissociates from eIF4E, allowing eIF4E to interact with eIF4G and translation initiation to resume. Because overexpression of eIF4E is linked to cellular transformation, 4E-BP is a tumor suppressor, and up-regulation of its activity is a goal of interest for cancer therapy. A recently discovered small molecule, eIF4E/eIF4G interaction inhibitor 1 (4EGI-1), disrupts the eIF4E/eIF4G interaction and promotes binding of 4E-BP1 to eIF4E. Structures of 14- to 16-residue 4E-BP fragments bound to eIF4E contain the eIF4E consensus binding motif, ⁵⁴YXXXXLΦ⁶⁰ (motif 1) but lack known phosphorylation sites. We report in this paper a 2.1-Å crystal structure of mouse eIF4E in complex with m⁷GTP and with a fragment of human 4E-BP1, extended C-terminally from the consensus-binding motif (4E-BP1_50–84). The extension, which includes a proline-turn-helix segment (motif 2) followed by a loop of irregular structure, reveals the location of two phosphorylation sites (S₆₅ and T₇₀). Our major finding is that the C-terminal extension (motif 3) is critical to 4E-BP1–mediated cell cycle arrest and that it partially overlaps with the binding site of 4EGI-1. Finally, the binding of 4E-BP1 and 4EGI-1 to eIF4E is therefore not mutually exclusive, and both ligands contribute to shift the equilibrium toward the inhibition of translation initiation.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Harvard Medical School, Boston, MA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); National Inst. of Health (NIH) (United States); Japan Society for the Promotion of Science (JSPS); Fonds de la Recherche en Santé au Québec (Canada); Alexander S. Onassis Public Benefit Foundation (Greece)

Grant/Contract Number:: AC02-06CH11357; P41 EB002026; CA68262; GM047467; GM103403

OSTI ID:: 1208688

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, Issue 30; ISSN 0027-8424

Publisher:: National Academy of Sciences, Washington, DC (United States)Copyright Statement

Country of Publication:: United States

Language:: ENGLISH

Citation Metrics:

Cited by: 68 works

Citation information provided by
Web of Science

References (56)

Autism-related deficits via dysregulated eIF4E-dependent translational control Gkogkas, Christos G.; Khoutorsky, Arkady; Ran, Israeli Nature, Vol. 493, Issue 7432 https://doi.org/10.1038/nature11628	journal	November 2012
eIF4 Initiation Factors: Effectors of mRNA Recruitment to Ribosomes and Regulators of Translation Gingras, Anne-Claude; Raught, Brian; Sonenberg, Nahum Annual Review of Biochemistry, Vol. 68, Issue 1 https://doi.org/10.1146/annurev.biochem.68.1.913	journal	June 1999
Electrostatics of nanosystems: Application to microtubules and the ribosome Baker, N. A.; Sept, D.; Joseph, S. Proceedings of the National Academy of Sciences, Vol. 98, Issue 18, p. 10037-10041 https://doi.org/10.1073/pnas.181342398	journal	August 2001
The translational repressor 4E-BP called to order by eIF4E: new structural insights by SAXS Gosselin, Pauline; Oulhen, Nathalie; Jam, Murielle Nucleic Acids Research, Vol. 39, Issue 8 https://doi.org/10.1093/nar/gkq1306	journal	December 2010
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 Paku, Keum Soon; Umenaga, Yu; Usui, Tsunego Biochemical Journal, Vol. 441, Issue 1 https://doi.org/10.1042/BJ20101481	journal	December 2011
Solving structures of protein complexes by molecular replacement with Phaser McCoy, Airlie J. Acta Crystallographica Section D Biological Crystallography, Vol. 63, Issue 1 https://doi.org/10.1107/S0907444906045975	journal	December 2006
4EGI-1 targets breast cancer stem cells by selective inhibition of translation that persists in CSC maintenance, proliferation and metastasis Yi, Tingfang; Kabha, Eihab; Papadopoulos, Evangelos Oncotarget, Vol. 5, Issue 15 https://doi.org/10.18632/oncotarget.2112	journal	June 2014
Clustal W and Clustal X version 2.0 Larkin, M. A.; Blackshields, G.; Brown, N. P. Bioinformatics, Vol. 23, Issue 21, p. 2947-2948 https://doi.org/10.1093/bioinformatics/btm404	journal	September 2007
A Quantitative Molecular Model for Modulation of Mammalian Translation by the eIF4E-binding Protein 1 Karim, Muhammad Manjurul; Hughes, John M. X.; Warwicker, Jim Journal of Biological Chemistry, Vol. 276, Issue 23 https://doi.org/10.1074/jbc.M011068200	journal	March 2001
Activation of translation complex eIF4F is essential for the genesis and maintenance of the malignant phenotype in human mammary epithelial cells Avdulov, Svetlana; Li, Shunan Cancer Cell, Vol. 5, Issue 6 https://doi.org/10.1016/j.ccr.2004.05.024	journal	June 2004
mRNA cap binding proteins: essential factors for initiating translation Shatkin, A. Cell, Vol. 40, Issue 2 https://doi.org/10.1016/0092-8674(85)90132-1	journal	February 1985
Casein Kinase 1 Promotes Cell Proliferation by Regulating mRNA Translation Shin, S.; Wolgamott, L.; Roux, P. P. Cancer Research, Vol. 74, Issue 1 https://doi.org/10.1158/0008-5472.CAN-13-1175	journal	November 2013
Crystal structure of a minimal eIF4E-Cup complex reveals a general mechanism of eIF4E regulation in translational repression Kinkelin, K.; Veith, K.; Grunwald, M. RNA, Vol. 18, Issue 9 https://doi.org/10.1261/rna.033639.112	journal	July 2012
Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism Gingras, A. -C.; Gygi, S. P.; Raught, B. Genes & Development, Vol. 13, Issue 11 https://doi.org/10.1101/gad.13.11.1422	journal	June 1999
Identification and function of the second eIF4E-binding region in N-terminal domain of eIF4G: Comparison with eIF4E-binding protein Umenaga, Yu; Paku, Keum Soon; In, Yasuko Biochemical and Biophysical Research Communications, Vol. 414, Issue 3 https://doi.org/10.1016/j.bbrc.2011.09.084	journal	October 2011
Regulation of Translation Initiation in Eukaryotes: Mechanisms and Biological Targets Sonenberg, Nahum; Hinnebusch, Alan G. Cell, Vol. 136, Issue 4 https://doi.org/10.1016/j.cell.2009.01.042	journal	February 2009
PROCHECK: a program to check the stereochemical quality of protein structures Laskowski, R. A.; MacArthur, M. W.; Moss, D. S. Journal of Applied Crystallography, Vol. 26, Issue 2 https://doi.org/10.1107/S0021889892009944	journal	April 1993
PHENIX : building new software for automated crystallographic structure determination Adams, Paul D.; Grosse-Kunstleve, Ralf W.; Hung, Li-Wei Acta Crystallographica Section D Biological Crystallography, Vol. 58, Issue 11 https://doi.org/10.1107/S0907444902016657	journal	October 2002
Crystallization of eIF4E complexed with eIF4GI peptide and glycerol reveals distinct structural differences around the cap-binding site Brown, Christopher J.; Verma, Chandra S.; Walkinshaw, Malcolm D. Cell Cycle, Vol. 8, Issue 12 https://doi.org/10.4161/cc.8.12.8742	journal	June 2009
Structure of the eukaryotic translation initiation factor eIF4E in complex with 4EGI-1 reveals an allosteric mechanism for dissociating eIF4G Papadopoulos, E.; Jenni, S.; Kabha, E. Proceedings of the National Academy of Sciences, Vol. 111, Issue 31 https://doi.org/10.1073/pnas.1410250111	journal	July 2014
mTORC1-Mediated Cell Proliferation, But Not Cell Growth, Controlled by the 4E-BPs Dowling, R. J. O.; Topisirovic, I.; Alain, T. Science, Vol. 328, Issue 5982 https://doi.org/10.1126/science.1187532	journal	May 2010
Importance of C-terminal flexible region of 4E-binding protein in binding with eukaryotic initiation factor 4E Mizuno, Atsuo; In, Yasuko; Fujita, Yuki FEBS Letters, Vol. 582, Issue 23-24 https://doi.org/10.1016/j.febslet.2008.09.003	journal	September 2008
Tumor suppression by small molecule inhibitors of translation initiation Chen, Limo; Aktas, Bertal H.; wang, Yibo Oncotarget, Vol. 3, Issue 8 https://doi.org/10.18632/oncotarget.598	journal	August 2012
Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 5' cap Lazaris-Karatzas, Anthoula; Montine, Kathleen S.; Sonenberg, Nahum Nature, Vol. 345, Issue 6275 https://doi.org/10.1038/345544a0	journal	June 1990
Glycogen synthase kinase-3β positively regulates protein synthesis and cell proliferation through the regulation of translation initiation factor 4E-binding protein 1 Shin, S.; Wolgamott, L.; Tcherkezian, J. Oncogene, Vol. 33, Issue 13 https://doi.org/10.1038/onc.2013.113	journal	April 2013
Inference of Macromolecular Assemblies from Crystalline State Krissinel, Evgeny; Henrick, Kim Journal of Molecular Biology, Vol. 372, Issue 3 https://doi.org/10.1016/j.jmb.2007.05.022	journal	September 2007
Highly efficient expression and purification system of small-size protein domains in Escherichia coli for biochemical characterization Bao, Wen-Jing; Gao, Yong-Guang; Chang, Yong-Gang Protein Expression and Purification, Vol. 47, Issue 2 https://doi.org/10.1016/j.pep.2005.11.021	journal	June 2006
Structural basis for mRNA Cap-Binding regulation of eukaryotic initiation factor 4E by 4E-binding protein, studied by spectroscopic, X-ray crystal structural, and molecular dynamics simulation methods Tomoo, Koji; Matsushita, Yasunori; Fujisaki, Hiroyuki Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1753, Issue 2 https://doi.org/10.1016/j.bbapap.2005.07.023	journal	December 2005
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, Isaac; Altmann, Michael; Sonenberg, Nahum Gene, Vol. 74, Issue 2 https://doi.org/10.1016/0378-1119(88)90184-9	journal	December 1988
Anti-oncogenic potential of the eIF4E-binding proteins Martineau, Y.; Azar, R.; Bousquet, C. Oncogene, Vol. 32, Issue 6 https://doi.org/10.1038/onc.2012.116	journal	April 2012
mTOR and S6K1 Mediate Assembly of the Translation Preinitiation Complex through Dynamic Protein Interchange and Ordered Phosphorylation Events Holz, Marina K.; Ballif, Bryan A.; Gygi, Steven P. Cell, Vol. 123, Issue 4 https://doi.org/10.1016/j.cell.2005.10.024	journal	November 2005
Cocrystal Structure of the Messenger RNA 5′ Cap-Binding Protein (eIF4E) Bound to 7-methyl-GDP Marcotrigiano, Joseph; Gingras, Anne-Claude; Sonenberg, Nahum Cell, Vol. 89, Issue 6 https://doi.org/10.1016/S0092-8674(00)80280-9	journal	June 1997
4E-BP3, a New Member of the Eukaryotic Initiation Factor 4E-binding Protein Family Poulin, Francis; Gingras, Anne-Claude; Olsen, Henrik Journal of Biological Chemistry, Vol. 273, Issue 22 https://doi.org/10.1074/jbc.273.22.14002	journal	May 1998
Application of iterative soft thresholding for fast reconstruction of NMR data non-uniformly sampled with multidimensional Poisson Gap scheduling Hyberts, Sven G.; Milbradt, Alexander G.; Wagner, Andreas B. Journal of Biomolecular NMR, Vol. 52, Issue 4 https://doi.org/10.1007/s10858-012-9611-z	journal	February 2012
Translational control in cancer Silvera, Deborah; Formenti, Silvia C.; Schneider, Robert J. Nature Reviews Cancer, Vol. 10, Issue 4 https://doi.org/10.1038/nrc2824	journal	April 2010
eIF-4E expression and its role in malignancies and metastases De Benedetti, Arrigo; Graff, Jeremy R. Oncogene, Vol. 23, Issue 18 https://doi.org/10.1038/sj.onc.1207545	journal	April 2004
Software Extensions to UCSF Chimera for Interactive Visualization of Large Molecular Assemblies Goddard, Thomas D.; Huang, Conrad C.; Ferrin, Thomas E. Structure, Vol. 13, Issue 3 https://doi.org/10.1016/j.str.2005.01.006	journal	March 2005
Ribosome Loading onto the mRNA Cap Is Driven by Conformational Coupling between eIF4G and eIF4E Gross, John D.; Moerke, Nathan J.; von der Haar, Tobias Cell, Vol. 115, Issue 6 https://doi.org/10.1016/S0092-8674(03)00975-9	journal	December 2003
Abstract 3891: NOSH-aspirin, a novel nitric oxide- and hydrogen sulfide-releasing hybrid, is a potent inhibitor of colon cancer cell growth Street, Cherease R.; Chattopadhyay, Mitali; Kodela, Ravinder Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL, Cancer Chemistry https://doi.org/10.1158/1538-7445.AM2012-3891	conference	November 2014
Structure of translation factor elF4E bound to m7GDP and interaction with 4E-binding protein Matsuo, Hiroshi; Li, Hanjun; McGuire, Abigail M. Nature Structural Biology, Vol. 4, Issue 9 https://doi.org/10.1038/nsb0997-717	journal	September 1997
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. Molecular and Cellular Biology, Vol. 15, Issue 9 https://doi.org/10.1128/MCB.15.9.4990	journal	September 1995
Poisson-Gap Sampling and Forward Maximum Entropy Reconstruction for Enhancing the Resolution and Sensitivity of Protein NMR Data Hyberts, Sven G.; Takeuchi, Koh; Wagner, Gerhard Journal of the American Chemical Society, Vol. 132, Issue 7 https://doi.org/10.1021/ja908004w	journal	February 2010
Molecular Architecture of 4E-BP Translational Inhibitors Bound to eIF4E Peter, Daniel; Igreja, Cátia; Weber, Ramona Molecular Cell, Vol. 57, Issue 6 https://doi.org/10.1016/j.molcel.2015.01.017	journal	March 2015
4E-BPs require non-canonical 4E-binding motifs and a lateral surface of eIF4E to repress translation Igreja, Cátia; Peter, Daniel; Weiler, Catrin Nature Communications, Vol. 5, Issue 1 https://doi.org/10.1038/ncomms5790	journal	September 2014
Prion formation correlates with activation of translation-regulating protein 4E-BP and neuronal transcription factor Elk1 Allard, Elin K.; Grujic, Mirjana; Fisone, Gilberto Neurobiology of Disease, Vol. 58 https://doi.org/10.1016/j.nbd.2013.05.014	journal	October 2013
Cap-Dependent Translation Initiation in Eukaryotes Is Regulated by a Molecular Mimic of eIF4G Marcotrigiano, Joseph; Gingras, Anne-Claude; Sonenberg, Nahum Molecular Cell, Vol. 3, Issue 6 https://doi.org/10.1016/S1097-2765(01)80003-4	journal	June 1999
Interaction of the Eukaryotic Initiation Factor 4E with 4E-BP2 at a Dynamic Bipartite Interface Lukhele, Sabelo; Bah, Alaji; Lin, Hong Structure, Vol. 21, Issue 12 https://doi.org/10.1016/j.str.2013.08.030	journal	December 2013
Folding of an intrinsically disordered protein by phosphorylation as a regulatory switch Bah, Alaji; Vernon, Robert M.; Siddiqui, Zeba Nature, Vol. 519, Issue 7541 https://doi.org/10.1038/nature13999	journal	December 2014
NMRPipe: A multidimensional spectral processing system based on UNIX pipes Delaglio, Frank; Grzesiek, Stephan; Vuister, GeertenW. Journal of Biomolecular NMR, Vol. 6, Issue 3 https://doi.org/10.1007/BF00197809	journal	November 1995
eIF4E – from translation to transformation Mamane, Yaël; Petroulakis, Emmanuel; Rong, Liwei Oncogene, Vol. 23, Issue 18 https://doi.org/10.1038/sj.onc.1207549	journal	April 2004
Multiple Mechanisms Control Phosphorylation of PHAS-I in Five (S/T)P Sites That Govern Translational Repression Mothe-Satney, I.; Yang, D.; Fadden, P. Molecular and Cellular Biology, Vol. 20, Issue 10 https://doi.org/10.1128/MCB.20.10.3558-3567.2000	journal	May 2000
Small-Molecule Inhibition of the Interaction between the Translation Initiation Factors eIF4E and eIF4G Moerke, Nathan J.; Aktas, Huseyin; Chen, Han Cell, Vol. 128, Issue 2 https://doi.org/10.1016/j.cell.2006.11.046	journal	January 2007
[20] Processing of X-ray diffraction data collected in oscillation mode Otwinowski, Zbyszek; Minor, Wladek Macromolecular Crystallography Part A, 307-326 https://doi.org/10.1016/S0076-6879(97)76066-X	book	January 1997
Rapamycin blocks the phosphorylation of 4E-BP1 and inhibits cap-dependent initiation of translation. Beretta, L.; Gingras, A. C.; Svitkin, Y. V. The EMBO Journal, Vol. 15, Issue 3 https://doi.org/10.1002/j.1460-2075.1996.tb00398.x	journal	February 1996
Hierarchical phosphorylation of the translation inhibitor 4E-BP1 Gingras, Anne-Claude; Raught, Brian; Gygi, Steven P. Genes & Development, Vol. 15, Issue 21 https://doi.org/10.1101/gad.912401	journal	November 2001
Translation Regulation as a Therapeutic Target in Cancer Grzmil, Michal; Hemmings, Brian A. Cancer Research, Vol. 72, Issue 16 https://doi.org/10.1158/0008-5472.CAN-12-0026	journal	August 2012

Cited By (20)

Mitosis-related phosphorylation of the eukaryotic translation suppressor 4E-BP1 and its interaction with eukaryotic translation initiation factor 4E (eIF4E) Sun, Rui; Cheng, Erdong; Velásquez, Celestino Journal of Biological Chemistry, Vol. 294, Issue 31 https://doi.org/10.1074/jbc.ra119.008512	journal	June 2019
Non-uniform sampling in quantitative assessment of heterogeneous solid-state NMR line shapes Burakova, Ekaterina; Vasa, Suresh K.; Klein, Alexander Journal of Biomolecular NMR, Vol. 74, Issue 1 https://doi.org/10.1007/s10858-019-00291-z	journal	December 2019
High throughput discovery of functional protein modifications by Hotspot Thermal Profiling Huang, Jun X.; Lee, Gihoon; Cavanaugh, Kate E. Nature Methods, Vol. 16, Issue 9 https://doi.org/10.1038/s41592-019-0499-3	journal	August 2019
The androgen receptor is a negative regulator of eIF4E phosphorylation at S209: implications for the use of mTOR inhibitors in advanced prostate cancer D'Abronzo, L. S.; Bose, S.; Crapuchettes, M. E. Oncogene, Vol. 36, Issue 46 https://doi.org/10.1038/onc.2017.233	journal	July 2017
The molecular choreography of protein synthesis: translational control, regulation, and pathways Chen, Jin; Choi, Junhong; O'Leary, Seán E. Quarterly Reviews of Biophysics, Vol. 49 https://doi.org/10.1017/s0033583516000056	journal	January 2016
Translational control of aberrant stress responses as a hallmark of cancer: Translational control of the tumour stress response El-Naggar, Amal M.; Sorensen, Poul H. The Journal of Pathology, Vol. 244, Issue 5 https://doi.org/10.1002/path.5030	journal	February 2018
Co-regulation of mRNA translation by TDP-43 and Fragile X Syndrome protein FMRP Majumder, Pritha; Chu, Jen-Fei; Chatterjee, Biswanath Acta Neuropathologica, Vol. 132, Issue 5 https://doi.org/10.1007/s00401-016-1603-8	journal	August 2016
IRES-mediated translation of foot-and-mouth disease virus (FMDV) in cultured cells derived from FMDV-susceptible and -insusceptible animals Kanda, Takehiro; Ozawa, Makoto; Tsukiyama-Kohara, Kyoko BMC Veterinary Research, Vol. 12, Issue 1 https://doi.org/10.1186/s12917-016-0694-8	journal	March 2016
Structural motifs in eIF4G and 4E-BPs modulate their binding to eIF4E to regulate translation initiation in yeast Grüner, Stefan; Weber, Ramona; Peter, Daniel Deutsches Elektronen-Synchrotron, DESY, Hamburg https://doi.org/10.3204/pubdb-2019-00020	text	January 2018
PEITC-mediated inhibition of mRNA translation is associated with both inhibition of mTORC1 and increased eIF2α phosphorylation in established cell lines and primary human leukemia cells. Yeomans, Alison; Lemm, Elizabeth; Wilmore, Sarah Impact Journals, LLC https://doi.org/10.17863/cam.74418	journalarticle	January 2016
Functional role of eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) in NSCLC Cao, Yueyu; Wei, Mengdan; Li, Bing Oncotarget, Vol. 7, Issue 17 https://doi.org/10.18632/oncotarget.8168	journal	March 2016
Structural basis for LeishIF4E-1 modulation by an interacting protein in the human parasite Leishmania major Meleppattu, Shimi; Arthanari, Haribabu; Zinoviev, Alexandra Nucleic Acids Research, Vol. 46, Issue 7 https://doi.org/10.1093/nar/gky194	journal	March 2018
Micropeptide CIP 2A‐ BP encoded by LINC 00665 inhibits triple‐negative breast cancer progression Guo, Binbin; Wu, Siqi; Zhu, Xun The EMBO Journal, Vol. 39, Issue 1 https://doi.org/10.15252/embj.2019102190	journal	November 2019
Noncanonical SQSTM1/p62-Nrf2 pathway activation mediates proteasome inhibitor resistance in multiple myeloma cells via redox, metabolic and translational reprogramming Riz, Irene; Hawley, Teresa S.; Marsal, Jeffrey W. Oncotarget, Vol. 7, Issue 41 https://doi.org/10.18632/oncotarget.11960	journal	September 2016
Mitotic protein kinase CDK1 phosphorylation of mRNA translation regulator 4E-BP1 Ser83 may contribute to cell transformation Velásquez, Celestino; Cheng, Erdong; Shuda, Masahiro Proceedings of the National Academy of Sciences, Vol. 113, Issue 30 https://doi.org/10.1073/pnas.1607768113	journal	July 2016
The 4E-BP growth pathway regulates the effect of ambient temperature on Drosophila metabolism and lifespan Carvalho, Gil B.; Drago, Ilaria; Hoxha, Sany Proceedings of the National Academy of Sciences, Vol. 114, Issue 36 https://doi.org/10.1073/pnas.1618994114	journal	August 2017
Characterization of the Expression of the RNA Binding Protein eIF4G1 and Its Clinicopathological Correlation with Serous Ovarian Cancer Li, Lanfang; Luo, Qingya; Xie, Zhe PLOS ONE, Vol. 11, Issue 9 https://doi.org/10.1371/journal.pone.0163447	journal	September 2016
Eukaryotic initiation factor 4E (eIF4E): A recap of the cap‐binding protein Batool, Asiya; Aashaq, Sabreena; Andrabi, Khurshid I. Journal of Cellular Biochemistry, Vol. 120, Issue 9 https://doi.org/10.1002/jcb.28851	journal	April 2019
A Conditionally Fluorescent Peptide Reporter of Secondary Structure Modulation Johnson, Oleta T.; Kaur, Tanpreet; Garner, Amanda L. ChemBioChem, Vol. 20, Issue 1 https://doi.org/10.1002/cbic.201800377	journal	October 2018
Profiling Reactive Metabolites via Chemical Trapping and Targeted Mass Spectrometry Chang, Jae Won; Lee, Gihoon; Coukos, John S. Analytical Chemistry, Vol. 88, Issue 13 https://doi.org/10.1021/acs.analchem.6b02009	journal	June 2016

Similar Records

Mitotic protein kinase CDK1 phosphorylation of mRNA translation regulator 4E-BP1 Ser83 may contribute to cell transformation

Journal Article · Mon Jul 11 00:00:00 EDT 2016 · Proceedings of the National Academy of Sciences of the United States of America · OSTI ID:1208688

Velasquez, Celestino; Cheng, Erdong; Shuda, Masahiro; +6 more

Inhibition of 4E-BP1 Sensitizes U87 Glioblastoma Xenograft Tumors to Irradiation by Decreasing Hypoxia Tolerance

Journal Article · Sun Mar 15 00:00:00 EDT 2009 · International Journal of Radiation Oncology, Biology and Physics · OSTI ID:1208688

Dubois, Ludwig; Magagnin, Michael G; Cleven, Arjen H.G.; +7 more

Overexpression of Phosphorylated 4E-BP1 Predicts for Tumor Recurrence and Reduced Survival in Cervical Carcinoma Treated With Postoperative Radiotherapy

Journal Article · Tue Dec 01 00:00:00 EST 2009 · International Journal of Radiation Oncology, Biology and Physics · OSTI ID:1208688

Benavente, Sergio; Verges, Ramona; Hermosilla, Eduardo; +5 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
translation initiation
phosphorylation
protein–protein interaction inhibitor
structure

Title: Molecular mechanism of the dual activity of 4EGI-1: Dissociating eIF4G from eIF4E but stabilizing the binding of unphosphorylated 4E-BP1

Citation Formats

References (56)

Cited By (20)

Similar Records

Related Subjects