Nahum Sonenberg

Summary

Affiliation: McGill University
Country: Canada

Publications

  1. pmc Epigenetic activation of a subset of mRNAs by eIF4E explains its effects on cell proliferation
    Yael Mamane
    Department of Biochemistry, McGill Cancer Centre, McGill University, Montreal, Quebec, Canada
    PLoS ONE 2:e242. 2007
  2. pmc A role for the eIF4E-binding protein 4E-T in P-body formation and mRNA decay
    Maria A Ferraiuolo
    Department of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada
    J Cell Biol 170:913-24. 2005
  3. pmc mTOR signaling: implications for cancer and anticancer therapy
    E Petroulakis
    Department of Biochemistry, McGill Cancer Centre, McGill University, 3655 Promenade Sir William Osler, Montreal, Que, Canada
    Br J Cancer 94:195-9. 2006
  4. pmc Control of translation and miRNA-dependent repression by a novel poly(A) binding protein, hnRNP-Q
    Yuri V Svitkin
    Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada
    PLoS Biol 11:e1001564. 2013
  5. pmc Remote control of gene function by local translation
    Hosung Jung
    Department of Anatomy, Brain Research Institute, and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120 752, South Korea
    Cell 157:26-40. 2014
  6. pmc Targeting adenosine monophosphate-activated protein kinase (AMPK) in preclinical models reveals a potential mechanism for the treatment of neuropathic pain
    Ohannes K Melemedjian
    Department of Pharmacology, University of Arizona, N Campbell Ave, Tucson, 85724, USA
    Mol Pain 7:70. 2011
  7. ncbi request reprint Eukaryotic translation initiation factors and regulators
    Nahum Sonenberg
    Department of Biochemistry and McGill Cancer Centre, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada
    Curr Opin Struct Biol 13:56-63. 2003
  8. ncbi request reprint Signal transduction. Protein synthesis and oncogenesis meet again
    Nahum Sonenberg
    Department of Biochemistry and McGill Cancer Centre, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6
    Science 314:428-9. 2006
  9. ncbi request reprint New modes of translational control in development, behavior, and disease
    Nahum Sonenberg
    Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada
    Mol Cell 28:721-9. 2007
  10. pmc Regulation of translation initiation in eukaryotes: mechanisms and biological targets
    Nahum Sonenberg
    Department of Biochemistry and Goodman Cancer Centre, McGill University, Montreal, Quebec, H3G 1Y6, Canada
    Cell 136:731-45. 2009

Detail Information

Publications134 found, 100 shown here

  1. pmc Epigenetic activation of a subset of mRNAs by eIF4E explains its effects on cell proliferation
    Yael Mamane
    Department of Biochemistry, McGill Cancer Centre, McGill University, Montreal, Quebec, Canada
    PLoS ONE 2:e242. 2007
    ..eIF4E, the mRNA 5' cap-binding protein, plays a major role in translational control. To understand how eIF4E affects cell proliferation and survival, we studied mRNA targets that are translationally responsive to eIF4E...
  2. pmc A role for the eIF4E-binding protein 4E-T in P-body formation and mRNA decay
    Maria A Ferraiuolo
    Department of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada
    J Cell Biol 170:913-24. 2005
    ..Collectively, these data suggest that 4E-T interaction with eIF4E is a priming event in inducing messenger ribonucleoprotein rearrangement and transition from translation to decay...
  3. pmc mTOR signaling: implications for cancer and anticancer therapy
    E Petroulakis
    Department of Biochemistry, McGill Cancer Centre, McGill University, 3655 Promenade Sir William Osler, Montreal, Que, Canada
    Br J Cancer 94:195-9. 2006
    ..Thus, inhibition of translation initiation through targeting the mTOR-signalling pathway is emerging as a promising therapeutic option...
  4. pmc Control of translation and miRNA-dependent repression by a novel poly(A) binding protein, hnRNP-Q
    Yuri V Svitkin
    Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada
    PLoS Biol 11:e1001564. 2013
    ..Thus, by competing with PABP, hnRNP-Q2 plays important roles in the regulation of global translation and miRNA-mediated repression of specific mRNAs...
  5. pmc Remote control of gene function by local translation
    Hosung Jung
    Department of Anatomy, Brain Research Institute, and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120 752, South Korea
    Cell 157:26-40. 2014
    ..Here, we discuss key findings in this area and possible implications of this adaptable and swift mechanism for spatial control of gene function. ..
  6. pmc Targeting adenosine monophosphate-activated protein kinase (AMPK) in preclinical models reveals a potential mechanism for the treatment of neuropathic pain
    Ohannes K Melemedjian
    Department of Pharmacology, University of Arizona, N Campbell Ave, Tucson, 85724, USA
    Mol Pain 7:70. 2011
    ..Therefore, injury-induced dysregulation of translation control underlies pathology leading to neuropathic pain and reveals AMPK as a novel therapeutic target for the potential treatment of neuropathic pain...
  7. ncbi request reprint Eukaryotic translation initiation factors and regulators
    Nahum Sonenberg
    Department of Biochemistry and McGill Cancer Centre, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada
    Curr Opin Struct Biol 13:56-63. 2003
    ....
  8. ncbi request reprint Signal transduction. Protein synthesis and oncogenesis meet again
    Nahum Sonenberg
    Department of Biochemistry and McGill Cancer Centre, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6
    Science 314:428-9. 2006
  9. ncbi request reprint New modes of translational control in development, behavior, and disease
    Nahum Sonenberg
    Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada
    Mol Cell 28:721-9. 2007
    ....
  10. pmc Regulation of translation initiation in eukaryotes: mechanisms and biological targets
    Nahum Sonenberg
    Department of Biochemistry and Goodman Cancer Centre, McGill University, Montreal, Quebec, H3G 1Y6, Canada
    Cell 136:731-45. 2009
    ....
  11. pmc mTORC1-mediated cell proliferation, but not cell growth, controlled by the 4E-BPs
    Ryan J O Dowling
    Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec H3A 1A3, Canada
    Science 328:1172-6. 2010
    ..Thus, control of cell size and cell cycle progression appear to be independent in mammalian cells, whereas in lower eukaryotes, 4E-BPs influence both cell growth and proliferation...
  12. pmc Mammalian miRNA RISC recruits CAF1 and PABP to affect PABP-dependent deadenylation
    Marc R Fabian
    Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada
    Mol Cell 35:868-80. 2009
    ..Importantly, we present evidence that GW182, a core component of the miRISC, directly interacts with PABP via its C-terminal region and that this interaction is required for miRNA-mediated deadenylation...
  13. pmc Regulation of poly(A) binding protein function in translation: Characterization of the Paip2 homolog, Paip2B
    Juan Jose Berlanga
    Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec, Canada
    RNA 12:1556-68. 2006
    ..Paip2A is more highly ubiquitinated than is Paip2B and is degraded more rapidly by the proteasome. Paip2 protein degradation may constitute a primary mechanism by which cells regulate PABP activity in translation...
  14. pmc Cap-dependent translational inhibition establishes two opposing morphogen gradients in Drosophila embryos
    Park F Cho
    Department of Biochemistry and McGill Cancer Center, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada
    Curr Biol 16:2035-41. 2006
    ..Thus, by regulating Cad and Hb expression, d4EHP plays a key role in establishing anterior-posterior axis polarity in the Drosophila embryo...
  15. doi request reprint Translational control of the innate immune response through IRF-7
    Rodney Colina
    Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec H3G 1Y6, Canada
    Nature 452:323-8. 2008
    ..These findings highlight the role of 4E-BPs as negative regulators of type-I IFN production, via translational repression of Irf7 mRNA...
  16. pmc The mTOR/PI3K and MAPK pathways converge on eIF4B to control its phosphorylation and activity
    David Shahbazian
    Department of Biochemistry, McGill Cancer Centre, McGill University, Montreal, Quebec, Canada
    EMBO J 25:2781-91. 2006
    ..Phosphorylation of eIF4B on Ser422 by RSK and S6K is physiologically significant, as it increases the interaction of eIF4B with the eukaryotic translation initiation factor 3...
  17. pmc Structural basis of ligand recognition by PABC, a highly specific peptide-binding domain found in poly(A)-binding protein and a HECT ubiquitin ligase
    Guennadi Kozlov
    Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada
    EMBO J 23:272-81. 2004
    ..The results provide insight into the specificity of PABC in mediating PABP-protein interactions...
  18. doi request reprint Control of synaptic plasticity and memory via suppression of poly(A)-binding protein
    Arkady Khoutorsky
    Department of Biochemistry and Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada
    Neuron 78:298-311. 2013
    ....
  19. pmc Translational control of the activation of transcription factor NF-κB and production of type I interferon by phosphorylation of the translation factor eIF4E
    Barbara Herdy
    Department of Biochemistry, McGill University, Montreal, Quebec, Canada
    Nat Immunol 13:543-50. 2012
    ..Thus, regulated phosphorylation of eIF4E has a key role in antiviral host defense by selectively controlling the translation of an mRNA that encodes a critical suppressor of the innate antiviral response...
  20. pmc Eukaryotic translation initiation factor 4E availability controls the switch between cap-dependent and internal ribosomal entry site-mediated translation
    Yuri V Svitkin
    Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6
    Mol Cell Biol 25:10556-65. 2005
    ..These data explain numerous reported observations where viral mRNAs are preferentially translated during infection...
  21. pmc Postnatal deamidation of 4E-BP2 in brain enhances its association with raptor and alters kinetics of excitatory synaptic transmission
    Michael Bidinosti
    Department of Biochemistry and Goodman Cancer Centre, McGill University, Montreal, QC H3G 1Y6, Canada
    Mol Cell 37:797-808. 2010
    ..4E-BP2 deamidation may represent a compensatory mechanism for the developmental reduction of PI3K-Akt-mTOR signaling...
  22. pmc Repair of isoaspartate formation modulates the interaction of deamidated 4E-BP2 with mTORC1 in brain
    Michael Bidinosti
    Department of Biochemistry and Goodman Cancer Centre, McGill University, Montreal, Quebec H3G 1Y6, Canada
    J Biol Chem 285:19402-8. 2010
    ..Further, we show that 4E-BP2 containing isoaspartates lacks the augmented association with raptor that is a feature of deamidated 4E-BP2...
  23. pmc RAS/ERK signaling promotes site-specific ribosomal protein S6 phosphorylation via RSK and stimulates cap-dependent translation
    Philippe P Roux
    Department of Pathology and Cell Biology, Institut de recherche en immunologie et en cancérologie IRIC, Universite de Montreal, Montreal, Quebec, Canada
    J Biol Chem 282:14056-64. 2007
    ..These data demonstrate that RSK provides an mTOR-independent pathway linking the Ras/ERK signaling cascade to the translational machinery...
  24. pmc Poly(A)-binding protein-interacting protein 1 binds to eukaryotic translation initiation factor 3 to stimulate translation
    Yvan Martineau
    Department of Biochemistry, McGill University, Montreal, Quebec, Canada
    Mol Cell Biol 28:6658-67. 2008
    ..Taken together, these data demonstrate that the eIF3-Paip1 interaction promotes translation. We propose that eIF3-Paip1 stabilizes the interaction between PABP and eIF4G, which brings about the circularization of the mRNA...
  25. doi request reprint Selective regulation of GluA subunit synthesis and AMPA receptor-mediated synaptic function and plasticity by the translation repressor 4E-BP2 in hippocampal pyramidal cells
    Israeli Ran
    Groupe de Recherche sur le Système Nerveux Central and Département de Physiologie, Universite de Montreal, Montreal, Quebec H3C 3J7, Canada
    J Neurosci 33:1872-86. 2013
    ..Thus, translational control through 4E-BP2 represents a unique mechanism for selective regulation of AMPAR synthesis, synaptic function, and long-term plasticity, important for hippocampal-dependent memory processes...
  26. doi request reprint A chemical genetic screen for mTOR pathway inhibitors based on 4E-BP-dependent nuclear accumulation of eIF4E
    Mark Livingstone
    Department of Biochemistry and McGill Cancer Centre, McGill University, Montreal, QC H3A 1A3, Canada
    Chem Biol 16:1240-9. 2009
    ..Using this assay in a small-scale screen, we have identified several compounds not previously known to inhibit mTOR signaling, demonstrating that this method can be adapted to larger screens...
  27. pmc The helicase protein DHX29 promotes translation initiation, cell proliferation, and tumorigenesis
    Armen Parsyan
    Department of Biochemistry, Faculty of Medicine and Goodman Cancer Center, McGill University, Montreal, Quebec, Canada
    Proc Natl Acad Sci U S A 106:22217-22. 2009
    ..DHX29 depletion also impedes cancer cell growth in culture and in xenografts. Thus, DHX29 is a bona fide translation initiation factor that potentially can be exploited as a target to inhibit cancer cell growth...
  28. ncbi request reprint mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translational regulation
    Masahiro Morita
    Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada
    Cell Metab 18:698-711. 2013
    ....
  29. pmc Control of eIF4E cellular localization by eIF4E-binding proteins, 4E-BPs
    Liwei Rong
    Department of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada
    RNA 14:1318-27. 2008
    ..A dramatic loss of nuclear 4E-BP1 occurs in c-Ha-Ras-expressing MEFs, which fail to show starvation-induced nuclear accumulation of eIF4E. Therefore, 4E-BP1 is a regulator of eIF4E cellular localization...
  30. pmc Poly(A) binding protein (PABP) homeostasis is mediated by the stability of its inhibitor, Paip2
    Madoka Yoshida
    Department of Biochemistry, McGill University, Montreal, Quebec, Canada
    EMBO J 25:1934-44. 2006
    ..Thus, we demonstrate that the turnover of Paip2 in the cell is mediated by EDD and is regulated by PABP. This mechanism serves as a homeostatic feedback to control the activity of PABP in cells...
  31. pmc Translational homeostasis via the mRNA cap-binding protein, eIF4E
    Akiko Yanagiya
    Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec H3A 1A3, Canada
    Mol Cell 46:847-58. 2012
    ..Thus, the activity of eIF4E is under homeostatic control via the regulation of the levels of its repressor protein 4E-BP1 through ubiquitination...
  32. pmc Control of cell survival and proliferation by mammalian eukaryotic initiation factor 4B
    David Shahbazian
    Department of Biochemistry and Goodman Cancer Centre, McGill University, The Cancer Research Building, 1160 Pine Avenue West, Room 615, Montreal, Quebec H3A 1A3, Canada
    Mol Cell Biol 30:1478-85. 2010
    ..These results demonstrate that eIF4B is required for cell proliferation and survival by regulating the translation of proliferative and prosurvival mRNAs...
  33. ncbi request reprint Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells
    Ryan J O Dowling
    Department of Biochemistry, McGill Cancer Centre, Montreal, Quebec, Canada
    Cancer Res 67:10804-12. 2007
    ..These results show that metformin-mediated AMPK activation leads to inhibition of mTOR and a reduction in translation initiation, thus providing a possible mechanism of action of metformin in the inhibition of cancer cell growth...
  34. pmc Complete translation of the hepatitis C virus genome in vitro: membranes play a critical role in the maturation of all virus proteins except for NS3
    Yuri V Svitkin
    Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6
    J Virol 79:6868-81. 2005
    ..Finally, the formyl-[35S]methionyl moiety of the initiator tRNA(Met) was incorporated exclusively into the core protein portion of the polyprotein, demonstrating that translation initiation in this system occurs with high fidelity...
  35. pmc Translational control of entrainment and synchrony of the suprachiasmatic circadian clock by mTOR/4E-BP1 signaling
    Ruifeng Cao
    Department of Biochemistry and Goodman Cancer Research Center, McGill University, Montreal, QC H3A 1A3, Canada
    Neuron 79:712-24. 2013
    ..These results reveal a key role for mTOR/4E-BP1-mediated translational control in regulating entrainment and synchrony of the master clock. ..
  36. pmc eIF2alpha phosphorylation bidirectionally regulates the switch from short- to long-term synaptic plasticity and memory
    Mauro Costa-Mattioli
    Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec, Canada
    Cell 129:195-206. 2007
    ..These findings highlight the importance of a single phosphorylation site in eIF2alpha as a key regulator of L-LTP and LTM formation...
  37. ncbi request reprint TOR is required for the retrograde regulation of synaptic homeostasis at the Drosophila neuromuscular junction
    Jay Penney
    Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada
    Neuron 74:166-78. 2012
    ..Our findings suggest that cap-dependent translation under the control of TOR plays a critical role in establishing the activity dependent homeostatic response at the NMJ...
  38. ncbi request reprint p53-dependent translational control of senescence and transformation via 4E-BPs
    Emmanuel Petroulakis
    Department of Biochemistry and Goodman Cancer Center, McGill University, Montreal, Quebec, H3G 1Y6, Canada
    Cancer Cell 16:439-46. 2009
    ..Our data demonstrate a role for 4E-BPs in senescence and tumorigenesis and highlight a p53-mediated mechanism of senescence through a 4E-BP-dependent pathway...
  39. pmc Stimulation of picornavirus replication by the poly(A) tail in a cell-free extract is largely independent of the poly(A) binding protein (PABP)
    Yuri V Svitkin
    Department of Biochemistry and McGill Cancer Centre, McGill University, Montreal, Quebec, Canada H3G 1Y6
    RNA 13:2330-40. 2007
    ..These results suggest that the poly(A) tail functions in picornavirus replication largely independent of PABP...
  40. pmc Vesicular stomatitis virus oncolysis is potentiated by impairing mTORC1-dependent type I IFN production
    Tommy Alain
    Department of Biochemistry and Goodman Cancer Center, McGill University, Montreal, QC H3G 1Y6, Canada
    Proc Natl Acad Sci U S A 107:1576-81. 2010
    ..These results demonstrate that reducing type I IFNs through inhibition of mTORC1 is an effective strategy to augment the therapeutic activity of VSV(DeltaM51)...
  41. doi request reprint miRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT
    Marc R Fabian
    Department of Biochemistry, McGill University, Montreal, Canada
    Nat Struct Mol Biol 18:1211-7. 2011
    ..Thus, GW182 serves as both a platform that recruits deadenylases and as a deadenylase coactivator that facilitates the removal of the poly(A) tail by CCR4-NOT...
  42. pmc A novel 4EHP-GIGYF2 translational repressor complex is essential for mammalian development
    Masahiro Morita
    Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada
    Mol Cell Biol 32:3585-93. 2012
    ..We propose a model by which the m4EHP-GIGYF2 complex represses translation of a subset of mRNAs during embryonic development, as was previously reported for d4EHP...
  43. doi request reprint Dissecting the role of mTOR: lessons from mTOR inhibitors
    Ryan J O Dowling
    Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, 1160 Pine Avenue West, Rm 609, Montreal, Quebec, Canada H3A 1A3
    Biochim Biophys Acta 1804:433-9. 2010
    ....
  44. ncbi request reprint A new paradigm for translational control: inhibition via 5'-3' mRNA tethering by Bicoid and the eIF4E cognate 4EHP
    Park F Cho
    Department of Biochemistry, McGill Cancer Center, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada
    Cell 121:411-23. 2005
    ..This example of cap-dependent translational control that is not mediated by canonical eIF4E defines a new paradigm for translational inhibition involving tethering of the mRNA 5' and 3' ends...
  45. pmc Eukaryotic initiation factor 4E-3 is essential for meiotic chromosome segregation, cytokinesis and male fertility in Drosophila
    Greco Hernández
    Department of Biology, McGill University, 3649 Promenade Sir William Osler, Montreal, Quebec, H3G 0B1, Canada
    Development 139:3211-20. 2012
    ..Our results imply that eIF4E-3 forms specific eIF4F complexes that are essential for spermatogenesis...
  46. doi request reprint eIF4E/4E-BP ratio predicts the efficacy of mTOR targeted therapies
    Tommy Alain
    Department of Biochemistry, SMBD Jewish General Hospital, Montreal, Quebec, Canada
    Cancer Res 72:6468-76. 2012
    ....
  47. pmc A mechanism of translational repression by competition of Paip2 with eIF4G for poly(A) binding protein (PABP) binding
    Muhammad M Karim
    Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, QC, Canada H3G 1Y6
    Proc Natl Acad Sci U S A 103:9494-9. 2006
    ..Thus, Paip2 can inhibit translation by a previously unrecognized mechanism, which is independent of its ability to disrupt PABP-poly(A) interaction...
  48. pmc Control of Paip1-eukayrotic translation initiation factor 3 interaction by amino acids through S6 kinase
    Yvan Martineau
    Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada
    Mol Cell Biol 34:1046-53. 2014
    ..We propose that S6K1/2 phosphorylate eIF3 to stimulate Paip1-eIF3 interaction and consequent translation initiation. Taken together, these data demonstrate that eIF3 is a new translation target of the mTOR/S6K pathway. ..
  49. ncbi request reprint MicroRNA inhibition of translation initiation in vitro by targeting the cap-binding complex eIF4F
    Geraldine Mathonnet
    Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec, Canada, H3G 1Y6
    Science 317:1764-7. 2007
    ..Our results indicate that inhibition of translation initiation is the earliest molecular event effected by miRNAs. Other mechanisms, such as mRNA degradation, may subsequently consolidate mRNA silencing...
  50. doi request reprint Leishmania repression of host translation through mTOR cleavage is required for parasite survival and infection
    Maritza Jaramillo
    Department of Biochemistry and Goodman Cancer Center, McGill University, Montreal, Quebec, Canada
    Cell Host Microbe 9:331-41. 2011
    ..This study demonstrates that Leishmania evolved a survival mechanism by activating 4E-BPs, which serve as major targets for host translational control...
  51. pmc Mextli is a novel eukaryotic translation initiation factor 4E-binding protein that promotes translation in Drosophila melanogaster
    Greco Hernández
    Department of Biology, McGill University, Montreal, Quebec, Canada
    Mol Cell Biol 33:2854-64. 2013
    ..Our results support the idea that Mxt, like eIF4G, coordinates the assembly of translation initiation complexes, rendering Mxt the first example of evolutionary convergence of eIF4G function. ..
  52. doi request reprint Translational control of long-lasting synaptic plasticity and memory
    Mauro Costa-Mattioli
    Department of Biochemistry and McGill Cancer Center, McGill University, Montreal QCH3G1Y6, Canada
    Neuron 61:10-26. 2009
    ..In this review, we summarize and discuss recent progress in the field and highlight the prospects for better understanding of long-lasting changes in synaptic strength, learning, and memory and implications for neurological diseases...
  53. ncbi request reprint A highly efficient and robust in vitro translation system for expression of picornavirus and hepatitis C virus RNA genomes
    Yuri V Svitkin
    Department of Biochemistry, McGill University, Montreal, Quebec, Canada
    Methods Enzymol 429:53-82. 2007
    ..With further optimization of cell-free conditions, the entire reconstitution of infectious HCV synthesis in vitro might become feasible...
  54. pmc The Drosophila poly(A) binding protein-interacting protein, dPaip2, is a novel effector of cell growth
    Guylaine Roy
    Department of Biochemistry and McGill Cancer Centre, McGill University, Montreal, Quebec H3G 1Y6, Canada
    Mol Cell Biol 24:1143-54. 2004
    ..We conclude that dPaip2 inhibits cell growth primarily by inhibiting protein synthesis...
  55. doi request reprint mRNA helicases: the tacticians of translational control
    Armen Parsyan
    Department of Biochemistry and Goodman Cancer Research Centre, Faculty of Medicine, McGill University, Montreal, Quebec H3A 1A3, Canada
    Nat Rev Mol Cell Biol 12:235-45. 2011
    ....
  56. pmc eIF4E phosphorylation promotes tumorigenesis and is associated with prostate cancer progression
    Luc Furic
    Goodman Cancer Centre and Department of Biochemistry, Cancer Pavilion, McGill University, Montreal, QC, Canada H3A 1A3
    Proc Natl Acad Sci U S A 107:14134-9. 2010
    ..Our findings establish eIF4E phosphorylation as a critical event in tumorigenesis. These findings raise the possibility that chemical compounds that prevent the phosphorylation of eIF4E could act as anticancer drugs...
  57. pmc General RNA-binding proteins have a function in poly(A)-binding protein-dependent translation
    Yuri V Svitkin
    Department of Biochemistry and Goodman Cancer Center, McGill University, Montreal, Quebec, Canada
    EMBO J 28:58-68. 2009
    ..Conversely, adding nonspecific RNA abrogated PABP stimulation of eIF4E binding. These data strongly suggest that competition between YB-1 and eIF4G for mRNA binding is required for efficient stimulation of eIF4F activity by PABP...
  58. pmc The poly(A)-binding protein partner Paip2a controls translation during late spermiogenesis in mice
    Akiko Yanagiya
    Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada
    J Clin Invest 120:3389-400. 2010
    ..We therefore propose a model whereby efficient mRNA translation in late spermiogenesis occurs at an optimal concentration of Pabp, a condition not fulfilled in Paip2a/Paip2b-DKO mice...
  59. doi request reprint The effects of adiponectin and metformin on prostate and colon neoplasia involve activation of AMP-activated protein kinase
    Mahvash Zakikhani
    Department of Oncology, McGill University, Montreal, Quebec, Canada
    Cancer Prev Res (Phila) 1:369-75. 2008
    ....
  60. ncbi request reprint An efficient system for cap- and poly(A)-dependent translation in vitro
    Yuri V Svitkin
    Department of Biochemistry, McGill University, Montreal, Quebec, Canada
    Methods Mol Biol 257:155-70. 2004
    ..Translation activity is restored to depleted extracts by the addition of recombinant PABP...
  61. pmc The Distribution of eIF4E-Family Members across Insecta
    Gritta Tettweiler
    Department of Biology, McGill University, 1205 Dr Penfield, Montreal, QC, Canada H3A 1B1
    Comp Funct Genomics 2012:960420. 2012
    ..melanogaster eIF4E-1. We also found that all insect species here analyzed contain only one Class II gene, termed 4E-HP. We discuss the possible evolutionary causes originating the multiplicity of eIF4E genes within the genus Drosophila...
  62. doi request reprint PABP interacting protein 2A (PAIP2A) regulates specific key proteins during spermiogenesis in the mouse
    Geraldine Delbes
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
    Biol Reprod 86:95. 2012
    ..Although several proteins affected by abrogation of Paip2a have established roles in reproduction, the roles of many others remain to be determined...
  63. pmc Requirement of RNA binding of mammalian eukaryotic translation initiation factor 4GI (eIF4GI) for efficient interaction of eIF4E with the mRNA cap
    Akiko Yanagiya
    Department of Biochemistry, McGill University, Montreal, Quebec, Canada
    Mol Cell Biol 29:1661-9. 2009
    ..These results demonstrate that eIF4GI serves to anchor eIF4E to the mRNA and enhance its interaction with the cap structure...
  64. pmc Signaling from Akt to FRAP/TOR targets both 4E-BP and S6K in Drosophila melanogaster
    Mathieu Miron
    Department of Biochemistry and McGill Cancer Center, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada
    Mol Cell Biol 23:9117-26. 2003
    ..Surprisingly, RNAi of dAkt also affected insulin-stimulated phosphorylation of dS6K, indicating that dAkt may also play a role in dS6K phosphorylation...
  65. pmc Structural analysis of 5'-mRNA-cap interactions with the human AGO2 MID domain
    Filipp Frank
    Department of Biochemistry, McGill University, 1160 Pine Avenue West, Montreal, Quebec H3A 1A3, Canada
    EMBO Rep 12:415-20. 2011
    ..Additionally, in vitro pull-down experiments with full-length hAGO2 indicate that the interaction with cap analogues is nonspecific...
  66. pmc Structural analysis of the DAP5 MIF4G domain and its interaction with eIF4A
    Geneviève Virgili
    Department of Biochemistry, McGill University, Montreal, QC H3G 0B1, Canada
    Structure 21:517-27. 2013
    ..This difference in stability of the complex may have functional implications in selecting the mode of translation initiation...
  67. ncbi request reprint Structural basis for 5'-nucleotide base-specific recognition of guide RNA by human AGO2
    Filipp Frank
    Department of Biochemistry, McGill University, Montreal, Quebec H3G 0B1, Canada
    Nature 465:818-22. 2010
    ..6 mM) or GMP (3.3 mM). This study provides structural evidence for nucleotide-specific interactions in the MID domain of eukaryotic AGO proteins and explains the observed preference for U or A at the 5' end of miRNAs...
  68. pmc Regulation of neuronal mRNA translation by CaM-kinase I phosphorylation of eIF4GII
    Taasin Srivastava
    Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239, USA
    J Neurosci 32:5620-30. 2012
    ....
  69. doi request reprint Persistent transcription- and translation-dependent long-term potentiation induced by mGluR1 in hippocampal interneurons
    Israeli Ran
    Groupe de Recherche sur le Système Nerveux Central and Département de Physiologie, Universite de Montreal, Montreal, Quebec H3C 3J7, Canada
    J Neurosci 29:5605-15. 2009
    ....
  70. pmc Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor, which acts via multiple mechanisms
    Avak Kahvejian
    Department of Biochemistry, McGill Cancer Center, McGill University, Montreal, Quebec, H3G 1Y6, Canada
    Genes Dev 19:104-13. 2005
    ..PABP can thus be considered a canonical translation initiation factor, integral to initiation complex formation at the 5'-end of mRNA...
  71. pmc Synergistic effects between analogs of DNA and RNA improve the potency of siRNA-mediated gene silencing
    Glen F Deleavey
    Department of Chemistry, McGill University, Montreal, QC, Canada
    Nucleic Acids Res 38:4547-57. 2010
    ..Chemical modification significantly reduced the immunostimulatory properties of these siRNAs in human peripheral blood mononuclear cells...
  72. pmc Pervasive and cooperative deadenylation of 3'UTRs by embryonic microRNA families
    Edlyn Wu
    Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal H3A 1A3 QC, Canada
    Mol Cell 40:558-70. 2010
    ..With this report, we reveal the extensive and direct impact of miRNA-mediated deadenylation on embryonic mRNAs...
  73. pmc Elevated sensitivity to diet-induced obesity and insulin resistance in mice lacking 4E-BP1 and 4E-BP2
    Olivier Le Bacquer
    Department of Biochemistry, McGill University, Montreal, Quebec, Canada
    J Clin Invest 117:387-96. 2007
    ..These data clearly demonstrate the role of 4E-BPs as a metabolic brake in the development of obesity and reinforce the idea that deregulated mTOR signaling is associated with the development of the metabolic syndrome...
  74. pmc Phosphorylation of eucaryotic translation initiation factor 4B Ser422 is modulated by S6 kinases
    Brian Raught
    Department of Biochemistry and McGill Cancer Centre, McGill University, Montreal, Quebec, Canada
    EMBO J 23:1761-9. 2004
    ..We therefore propose that eIF4B may mediate some of the effects of the S6Ks on translation...
  75. doi request reprint Current status and challenges associated with targeting mTOR for cancer therapy
    Ryan J O Dowling
    Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec, Canada
    BioDrugs 23:77-91. 2009
    ..In this review, we summarize the use of sirolimus derivatives in clinical trials and address some of the challenges associated with targeting mTOR for the treatment of human cancer...
  76. pmc Crystallization and preliminary X-ray diffraction analysis of the middle domain of Paip1
    Ahmad Seif Kanaan
    Department of Biochemistry, McGill University, Montreal, Quebec, Canada
    Acta Crystallogr Sect F Struct Biol Cryst Commun 65:1060-4. 2009
    ..Here, the crystallization and preliminary diffraction analysis of the middle domain of Paip1 (Paip1M), which produces crystals that diffract to a resolution of 2.2 A, are presented...
  77. doi request reprint Translational control of gene expression: a molecular switch for memory storage
    Mauro Costa-Mattioli
    Department of Biochemistry and McGill Cancer Center, 3655 Promendde Sir William Osler, McGill University, Montreal, QC H3G 1Y6, Canada
    Prog Brain Res 169:81-95. 2008
    ..In this chapter, we provide an overview of the role of translational control by the eIF2alpha signaling pathway in long-term synaptic plasticity and memory consolidation...
  78. pmc La autoantigen is necessary for optimal function of the poliovirus and hepatitis C virus internal ribosome entry site in vivo and in vitro
    Mauro Costa-Mattioli
    Department of Biochemistry and McGill Cancer Center, McGill University, McIntyre Medical Building, Montreal, Quebec, Canada H3G 1Y6
    Mol Cell Biol 24:6861-70. 2004
    ..These results provide strong evidence for a function of the La autoantigen in IRES-dependent translation and define the step of translation which is stimulated by La...
  79. pmc Translational control of hippocampal synaptic plasticity and memory by the eIF2alpha kinase GCN2
    Mauro Costa-Mattioli
    Department of Biochemistry and McGill Cancer Center, Montreal, Quebec, Canada
    Nature 436:1166-73. 2005
    ..Our study provides genetic, physiological, behavioural and molecular evidence that GCN2 regulates synaptic plasticity, as well as learning and memory, through modulation of the ATF4/CREB pathway...
  80. doi request reprint Cap and cap-binding proteins in the control of gene expression
    Ivan Topisirovic
    Department of Biochemistry and Goodman Cancer Centre, McGill University, Montreal, QC, Canada
    Wiley Interdiscip Rev RNA 2:277-98. 2011
    ..We also describe emerging regulatory pathways that control mRNA capping and cap-binding proteins in the cell...
  81. pmc Vesicular stomatitis virus oncolysis of T lymphocytes requires cell cycle entry and translation initiation
    Stephanie Oliere
    Molecular Oncology Group, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Canada H3T 1E2
    J Virol 82:5735-49. 2008
    ..These results demonstrate that VSV replication in primary T lymphocytes relies on cell cycle transition from the G(0) phase to the G(1) phase, which is characterized by a sharp increase in ribogenesis and protein synthesis...
  82. ncbi request reprint Inhibitory properties of nucleic acid-binding ligands on protein synthesis
    Abba Malina
    Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, Que, Canada H3G 1Y6
    FEBS Lett 579:79-89. 2005
    ..We used this information to identify a novel threading intercalator that inhibits Hepatitis C virus internal initiation...
  83. pmc Starvation and oxidative stress resistance in Drosophila are mediated through the eIF4E-binding protein, d4E-BP
    Gritta Tettweiler
    Department of Biology, McGill University, Montreal, Quebec, Canada
    Genes Dev 19:1840-3. 2005
    ..Thus, d4E-BP is an important downstream effector of a dFOXO phenotype, and regulation of translation by eIF4E is vital during environmental stress...
  84. pmc The leader of human immunodeficiency virus type 1 genomic RNA harbors an internal ribosome entry segment that is active during the G2/M phase of the cell cycle
    Ann Brasey
    Biochemistry Department, McGill University, H3G 1Y6 Montreal, Canada
    J Virol 77:3939-49. 2003
    ..These data strongly suggest that, as for HIV-1 transcription, IRES-mediated translation initiation could play an important role in virus replication during virus-induced G(2)/M cell cycle arrest...
  85. ncbi request reprint Translational control of long-term synaptic plasticity and memory storage by eIF2alpha
    Mauro Costa-Mattioli
    Department of Biochemistry, McGill Cancer Centre, Montreal, Quebec, Canada
    Crit Rev Neurobiol 18:187-95. 2006
    ..In this review, we highlight the role of the eukaryotic initiation factor 2 alpha (eIF2alpha) signalling pathway in long-term synaptic plasticity and memory...
  86. ncbi request reprint eIF4E, the mRNA cap-binding protein: from basic discovery to translational research
    Nahum Sonenberg
    Department of Biochemistry and McGill Cancer Centre, McGill University, Montreal, QC H3G1Y6, Canada
    Biochem Cell Biol 86:178-83. 2008
    ..In this article I describe the discovery of eIF4E, its mechanism of action in translation initiation, and its role in the control of cancer and innate immunity...
  87. doi request reprint Understanding how miRNAs post-transcriptionally regulate gene expression
    Marc R Fabian
    Department of Biochemistry, McGill University, Montreal, QC, H3G 1A1, Canada
    Prog Mol Subcell Biol 50:1-20. 2010
    ..Recent reports suggest that many miRNA effects are mediated through proteins of the GW182 family. This chapter focuses on the multiple and potentially overlapping mechanisms that miRNAs utilize to regulate gene expression in eukaryotes...
  88. ncbi request reprint Coordinated transcriptional and translational control in metabolic homeostasis in flies
    Paul Lasko
    Department of Biology and Developmental Biology Research Initiative, McGill University, Montreal, Quebec H3A 1B1, Canada
    Genes Dev 21:235-7. 2007
  89. ncbi request reprint Translational control by the eukaryotic ribosome
    Ivan Topisirovic
    Lady Davis Institute for Medical Research, Sir Mortimer B Davis Jewish General Hospital, McGill University, Montreal, Quebec, Canada
    Cell 145:333-4. 2011
    ....
  90. ncbi request reprint Regulation of mRNA translation and stability by microRNAs
    Marc Robert Fabian
    Department of Biochemistry and Goodman Cancer Research Center, McGill University, Montreal, Quebec, H3G 1Y6, Canada
    Annu Rev Biochem 79:351-79. 2010
    ..We also address the issue of cellular localization of miRNA-mediated events and a role for RNA-binding proteins in activation or relief of miRNA repression...
  91. pmc Cell-free synthesis of encephalomyocarditis virus
    Yuri V Svitkin
    Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec, Canada H3G 1Y6
    J Virol 77:6551-5. 2003
    ..Excess input RNA impaired RNA replication and virus production but not translation. This suggests the existence of a negative-feedback mechanism for regulation of RNA replication by the viral plus-strand RNA or proteins...
  92. doi request reprint An efficient system for let-7 microRNA and GW182 protein-mediated deadenylation in vitro
    Marc R Fabian
    Department of Biochemistry, Goodman Cancer Research Center, McGill University, Montreal, QC, Canada
    Methods Mol Biol 725:207-17. 2011
    ..As an example, the protocol for assaying let-7 and GW182 (TNRC6) protein-mediated deadenylation of mRNA in vitro is described...
  93. pmc Human rhinovirus 2A proteinase cleavage sites in eukaryotic initiation factors (eIF) 4GI and eIF4GII are different
    Alessandra Gradi
    Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec, Canada H3G 1Y6
    J Virol 77:5026-9. 2003
    ..Here, we identify the human rhinovirus 2 2A(pro) cleavage site in eIF4GII in vitro as PLLNV(699)*GSR; this sequence lies seven amino acids C-terminal to the cleavage site previously identified in eIF4GI (LSTR681*GPP)...
  94. pmc Paip1 interacts with poly(A) binding protein through two independent binding motifs
    Guylaine Roy
    Department of Biochemistry and McGill Cancer Centre, McGill University, Montreal, Quebec, Canada H3G 1Y6
    Mol Cell Biol 22:3769-82. 2002
    ..PABP also contains two Paip1 binding sites, one located in RNA recognition motifs 1 and 2 and the other located in the C-terminal domain. Paip1 binds to PABP with a 1:1 stoichiometry and an apparent K(d) of 1.9 nM...
  95. ncbi request reprint Activation of GCN2 in UV-irradiated cells inhibits translation
    Jing Deng
    Department of Biochemistry and McGill Cancer Centre, McGill University, 3655 Promenade Sir William Osler, Montreal, H3G 1Y6, Quebec, Canada
    Curr Biol 12:1279-86. 2002
    ..While the effects of UV irradiation on DNA replication and transcription have been extensively studied, the mechanism(s) responsible for translational repression are poorly understood...
  96. pmc Phosphorylation of eukaryotic translation initiation factor 4E is critical for growth
    Pascal E D Lachance
    Department of Biology, McGill University, 1205 Ave Docteur Penfield, Montreal, Quebec, Canada H3A 1B1
    Mol Cell Biol 22:1656-63. 2002
    ..Escapers develop more slowly than control siblings and are smaller. These genetic data provide evidence that eIF4E phosphorylation is biologically significant and is essential for normal growth and development...
  97. pmc Resistance to vesicular stomatitis virus infection requires a functional cross talk between the eukaryotic translation initiation factor 2alpha kinases PERK and PKR
    Dionissios Baltzis
    Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Côte Ste Catherine St, Montreal, Quebec H3T 1E2, Canada
    J Virol 78:12747-61. 2004
    ..These findings further implicate PERK in virus infection, and provide evidence that the antiviral and antiapoptotic roles of PERK are mediated, at least in part, via the activation of PKR...
  98. ncbi request reprint Mechanisms governing the control of mRNA translation
    Mark Livingstone
    Department of Biochemistry and McGill Cancer Centre, McGill University, Montreal, QC H3A 1A3, Canada
    Phys Biol 7:021001. 2010
    ....
  99. pmc Stimulation of mammalian translation initiation factor eIF4A activity by a small molecule inhibitor of eukaryotic translation
    Marie Eve Bordeleau
    Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, QC, Canada H3G 1Y6
    Proc Natl Acad Sci U S A 102:10460-5. 2005
    ..Our results suggest that proper control of eIF4A helicase activity is necessary for efficient ribosome binding and demonstrate the feasibility of selectively targeting DEAD-box RNA helicases with small molecules...

Research Grants7

  1. Translational control by poly(A)-binding protein and its modulators (Paips)
    Nahum Sonenberg; Fiscal Year: 2010
    ..Poly(A) binding protein binds to the tail of the genetic material (messenger RNA) that serves as template for the synthesis of all proteins in the cell. ..
  2. Regulation of mRNA 5'-3' interactions: The role of Paips
    Nahum Sonenberg; Fiscal Year: 2002
    ..In the case of Paip2A and Paip2B, which are functional homologs, a Paip2AIPaip2B KO mouse will be generated. KO mice will be analyzed for phenotypic abnormalities. ..
  3. Regulation of mRNA 5'-3' interactions: The role of Paips
    Nahum Sonenberg; Fiscal Year: 2003
    ..In the case of Paip2A and Paip2B, which are functional homologs, a Paip2AIPaip2B KO mouse will be generated. KO mice will be analyzed for phenotypic abnormalities. ..
  4. Regulation of mRNA 5'-3' interactions: The role of Paips
    Nahum Sonenberg; Fiscal Year: 2004
    ..In the case of Paip2A and Paip2B, which are functional homologs, a Paip2AIPaip2B KO mouse will be generated. KO mice will be analyzed for phenotypic abnormalities. ..
  5. Regulation of mRNA 5'-3' interactions: The role of Paips
    Nahum Sonenberg; Fiscal Year: 2005
    ..In the case of Paip2A and Paip2B, which are functional homologs, a Paip2AIPaip2B KO mouse will be generated. KO mice will be analyzed for phenotypic abnormalities. ..
  6. Translational control by poly(A)-binding protein and its modulators (Paips)
    Nahum Sonenberg; Fiscal Year: 2009
    ..Poly(A) binding protein binds to the tail of the genetic material (messenger RNA) that serves as template for the synthesis of all proteins in the cell. ..