Christopher G Proud

Summary

Affiliation: University of Southampton
Country: UK

Publications

  1. doi request reprint mTORC1 signalling and mRNA translation
    Christopher G Proud
    School of Biological Sciences, University of Southampton, Southampton SO16 7PX, UK
    Biochem Soc Trans 37:227-31. 2009
  2. ncbi request reprint A new link in the chain from amino acids to mTORC1 activation
    Chris G Proud
    Centre for Biological Sciences, Life Sciences Building B85, University of Southampton, Southampton SO17 1BJ, UK
    Mol Cell 44:7-8. 2011
  3. pmc mTOR signaling regulates the processing of pre-rRNA in human cells
    Valentina Iadevaia
    School of Biological Sciences, University of Southampton, SO17 1BJ, UK
    Nucleic Acids Res 40:2527-39. 2012
  4. pmc Insights into the regulation of eukaryotic elongation factor 2 kinase and the interplay between its domains
    Craig R Pigott
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada
    Biochem J 442:105-18. 2012
  5. pmc Identification of autophosphorylation sites in eukaryotic elongation factor-2 kinase
    Sebastien Pyr dit Ruys
    Universite Catholique de Louvain, Brussels, Belgium
    Biochem J 442:681-92. 2012
  6. doi request reprint mTORC1 regulates the efficiency and cellular capacity for protein synthesis
    Christopher G Proud
    Centre for Biological Sciences, University of Southampton, Life Sciences Building B85, Southampton, SO17 1BJ, UK
    Biochem Soc Trans 41:923-6. 2013
  7. pmc mTOR direct interactions with Rheb-GTPase and raptor: sub-cellular localization using fluorescence lifetime imaging
    Rahul B Yadav
    Central Laser Facility, STFC, Rutherford Appleton Laboratory, Research Complex at Harwell, Didcot, Oxon OX110QX, UK
    BMC Cell Biol 14:3. 2013
  8. doi request reprint mTOR Signalling in Health and Disease
    Christopher G Proud
    School of Biological Sciences, Life Sciences Building, University of Southampton, Southampton SO17 1BJ, UK
    Biochem Soc Trans 39:431-6. 2011
  9. ncbi request reprint Dynamic balancing: DEPTOR tips the scales
    Christopher G Proud
    School of Biological Sciences, University of Southampton, Southampton SO16 7PX, UK
    J Mol Cell Biol 1:61-3. 2009
  10. doi request reprint The binding of PRAS40 to 14-3-3 proteins is not required for activation of mTORC1 signalling by phorbol esters/ERK
    Bruno D Fonseca
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC V6T1Z3, Canada
    Biochem J 411:141-9. 2008

Collaborators

Detail Information

Publications44

  1. doi request reprint mTORC1 signalling and mRNA translation
    Christopher G Proud
    School of Biological Sciences, University of Southampton, Southampton SO16 7PX, UK
    Biochem Soc Trans 37:227-31. 2009
    ..However, there are still important gaps in our understanding of the actions of mTORC1 and the relative contributions that different targets of mTORC1 make to the activation of protein synthesis remain to be established...
  2. ncbi request reprint A new link in the chain from amino acids to mTORC1 activation
    Chris G Proud
    Centre for Biological Sciences, Life Sciences Building B85, University of Southampton, Southampton SO17 1BJ, UK
    Mol Cell 44:7-8. 2011
    ..A recent study reveals that the scaffold protein p62 plays a role in linking nutritional cues (amino acids) to the activation of mammalian target of rapamycin complex 1 (mTORC1), a protein kinase that controls cell size and proliferation...
  3. pmc mTOR signaling regulates the processing of pre-rRNA in human cells
    Valentina Iadevaia
    School of Biological Sciences, University of Southampton, SO17 1BJ, UK
    Nucleic Acids Res 40:2527-39. 2012
    ..These data show that mTORC1 is located in nucleoli where it acts to regulate events involved in ribosome biogenesis including the maturation of rRNA molecules...
  4. pmc Insights into the regulation of eukaryotic elongation factor 2 kinase and the interplay between its domains
    Craig R Pigott
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada
    Biochem J 442:105-18. 2012
    ..On the basis of these findings, we propose a model for the functional organization and control of eEF2K...
  5. pmc Identification of autophosphorylation sites in eukaryotic elongation factor-2 kinase
    Sebastien Pyr dit Ruys
    Universite Catholique de Louvain, Brussels, Belgium
    Biochem J 442:681-92. 2012
    ..Ser(366) phosphorylation was also detected in intact cells, but was still observed in the kinase-inactive construct, demonstrating that this site is phosphorylated not only autocatalytically but also in trans by other kinases...
  6. doi request reprint mTORC1 regulates the efficiency and cellular capacity for protein synthesis
    Christopher G Proud
    Centre for Biological Sciences, University of Southampton, Life Sciences Building B85, Southampton, SO17 1BJ, UK
    Biochem Soc Trans 41:923-6. 2013
    ..Taken together, these effects allow mTORC1 signalling to drive cell growth and proliferation. ..
  7. pmc mTOR direct interactions with Rheb-GTPase and raptor: sub-cellular localization using fluorescence lifetime imaging
    Rahul B Yadav
    Central Laser Facility, STFC, Rutherford Appleton Laboratory, Research Complex at Harwell, Didcot, Oxon OX110QX, UK
    BMC Cell Biol 14:3. 2013
    ....
  8. doi request reprint mTOR Signalling in Health and Disease
    Christopher G Proud
    School of Biological Sciences, Life Sciences Building, University of Southampton, Southampton SO17 1BJ, UK
    Biochem Soc Trans 39:431-6. 2011
    ....
  9. ncbi request reprint Dynamic balancing: DEPTOR tips the scales
    Christopher G Proud
    School of Biological Sciences, University of Southampton, Southampton SO16 7PX, UK
    J Mol Cell Biol 1:61-3. 2009
    ..A recent study identifies a new partner and regulator of mTOR, which can alter the balance of signaling downstream of mTOR and appears to be important in certain cancers, such as multiple myelomas...
  10. doi request reprint The binding of PRAS40 to 14-3-3 proteins is not required for activation of mTORC1 signalling by phorbol esters/ERK
    Bruno D Fonseca
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC V6T1Z3, Canada
    Biochem J 411:141-9. 2008
    ..Indeed, our results suggest that PRAS40 may not actually be involved in controlling mTORC1, but rather be a downstream target of mTORC1 that is regulated in response only to specific stimuli, such as insulin...
  11. ncbi request reprint Analysis of the regulatory motifs in eukaryotic initiation factor 4E-binding protein 1
    Vivian H Y Lee
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada
    FEBS J 275:2185-99. 2008
    ..These data provide important information on the structural requirements for efficient signalling downstream of mTORC1...
  12. ncbi request reprint PRAS40 is a target for mammalian target of rapamycin complex 1 and is required for signaling downstream of this complex
    Bruno D Fonseca
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 282:24514-24. 2007
    ..However, this has no effect on the phosphorylation of Akt or TSC2 (an Akt substrate). These data place PRAS40 downstream of mTORC1 but upstream of its effectors, such as S6K1 and 4E-BP1...
  13. pmc Re-evaluating the roles of proposed modulators of mammalian target of rapamycin complex 1 (mTORC1) signaling
    Xuemin Wang
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver V6T 1Z3, Canada
    J Biol Chem 283:30482-92. 2008
    ..Our data also indicate that, in the mammalian cell lines tested here, neither TCTP nor FKBP38 regulates mTORC1 signaling...
  14. doi request reprint Blocking eukaryotic initiation factor 4F complex formation does not inhibit the mTORC1-dependent activation of protein synthesis in cardiomyocytes
    Brandon P H Huang
    Department of Biochemistry and Molecular Biology, University of British Columbia and Diabetes Research Group, Life Sciences Institute, Vancouver, Canada
    Am J Physiol Heart Circ Physiol 296:H505-14. 2009
    ..Therefore, other mTORC1 targets are more important in the inhibition by rapamycin of the rapid activation of protein synthesis and of cell growth...
  15. doi request reprint Rheb activates protein synthesis and growth in adult rat ventricular cardiomyocytes
    Yanni Wang
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada
    J Mol Cell Cardiol 45:812-20. 2008
    ..Our findings reveal that Rheb itself can activate both protein synthesis and cell growth in ARVC and demonstrate the key role played by mTORC1 in the growth of cardiomyocytes...
  16. ncbi request reprint Roles of the mammalian target of rapamycin, mTOR, in controlling ribosome biogenesis and protein synthesis
    Valentina Iadevaia
    School of Biological Sciences, Life Sciences Building, Highfield Campus, University of Southampton, Southampton SO17 1BJ, UK
    Biochem Soc Trans 40:168-72. 2012
    ..We found that mTORC1 also regulates the processing of the precursors of rRNA. mTORC1 thus co-ordinates several steps in ribosome biogenesis...
  17. doi request reprint Stable isotope-labelling analysis of the impact of inhibition of the mammalian target of rapamycin on protein synthesis
    Yilin Huo
    Centre for Biological Sciences, University of Southampton, UK
    Biochem J 444:141-51. 2012
    ..Lastly, a SILAC-based approach revealed that, although rapamycin and mTOR-KIs have little effect on general protein stability, they stabilize proteins encoded by 5'-TOP mRNAs...
  18. pmc Impairing the production of ribosomal RNA activates mammalian target of rapamycin complex 1 signalling and downstream translation factors
    Rui Liu
    Centre for Biological Sciences, University of Southampton, Highfield Campus, Southampton SO17 1BJ, UK, Centre de Recherche en Nutrition Humaine, INRA Clermont Theix, Unite de Nutrition Humaine, 63122 Ceyrat, France and Division of Molecular Physiology, James Black Centre, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK
    Nucleic Acids Res 42:5083-96. 2014
    ..Therefore, our data demonstrate that disrupting rRNA production activates mTORC1 signalling to enhance the efficiency of the translational machinery, likely to help compensate for impaired ribosome production. ..
  19. doi request reprint The C-terminal domain of Mnk1a plays a dual role in tightly regulating its activity
    Susan Goto
    Department of Biochemistry and Molecular Biology and the Diabetes Research Group, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada
    Biochem J 423:279-90. 2009
    ..These studies help to identify the features that give rise to the diverse properties of human Mnk isoforms...
  20. doi request reprint Evaluation of mTOR-regulated mRNA translation
    Valentina Iadevaia
    School of Biological Sciences, University of Southampton, Southampton, UK
    Methods Mol Biol 821:171-85. 2012
    ..A method for the separation of polysomes from non-polysomal mRNAs is described...
  21. doi request reprint Rapamycin enhances eIF4E phosphorylation by activating MAP kinase-interacting kinase 2a (Mnk2a)
    Rebecca L Stead
    Centre for Biological Sciences, Building 85, University of Southampton, Southampton SO17 1BJ, United Kingdom
    FEBS Lett 587:2623-8. 2013
    ..Our findings have potentially important implications for the use of rapamycin and its analogues in cancer therapy, suggesting that inhibitors of mTOR and Mnk (or Mnk2) may be more efficacious than rapalogs alone. ..
  22. ncbi request reprint Methods for studying signal-dependent regulation of translation factor activity
    Xuemin Wang
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada
    Methods Enzymol 431:113-42. 2007
    ..In addition, we provide guidelines on using small molecule inhibitors to assess the involvement of specific signaling pathways in controlling translation factors and protein synthesis...
  23. ncbi request reprint Control of the translational machinery by amino acids
    Christopher G Proud
    Centre for Biological Sciences, University of Southampton, Southampton, United Kingdom
    Am J Clin Nutr 99:231S-236S. 2014
    ..This process shuts down general protein synthesis to conserve amino acids. ..
  24. pmc Screen for chemical modulators of autophagy reveals novel therapeutic inhibitors of mTORC1 signaling
    Aruna D Balgi
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada
    PLoS ONE 4:e7124. 2009
    ..Addressing the therapeutic potential of modulating mTORC1 signaling and autophagy in human disease requires active chemicals with pharmacologically desirable properties...
  25. pmc A novel mechanism for the control of translation initiation by amino acids, mediated by phosphorylation of eukaryotic initiation factor 2B
    Xuemin Wang
    Department of Biochemistry and Molecular Biology, University of British Columbia, Life Sciences Centre, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada
    Mol Cell Biol 28:1429-42. 2008
    ..These findings identify a new way in which amino acids regulate a key step in translation initiation and indicate that this involves a novel amino acid-sensitive signaling mechanism...
  26. ncbi request reprint Cell signaling. mTOR, unleashed
    Christopher G Proud
    Department of Biochemistry and Molecular Biology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia V6T 1Z3, Canada
    Science 318:926-7. 2007
  27. doi request reprint p90(RSK)s mediate the activation of ribosomal RNA synthesis by the hypertrophic agonist phenylephrine in adult cardiomyocytes
    Ze Zhang
    Centre for Biological Sciences, University of Southampton, Southampton, UK
    J Mol Cell Cardiol 59:139-47. 2013
    ..This is important both for our understanding of the mechanisms that control ribosome production and, potentially, for the management of cardiac hypertrophy...
  28. ncbi request reprint mTORC1 signaling: what we still don't know
    Xuemin Wang
    School of Biological Sciences, Life Sciences Building, University of Southampton, UK
    J Mol Cell Biol 3:206-20. 2011
    ....
  29. doi request reprint Natural product-derived antitumor compound phenethyl isothiocyanate inhibits mTORC1 activity via TSC2
    Breeze E Cavell
    Cancer Research UK Centre, Cancer Sciences Unit, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, SO16 6YD, UK
    J Nat Prod 75:1051-7. 2012
    ..This is dependent on the presence of TSC2, and inhibition of mTORC1 contributes to optimal 1-induced growth inhibition. Inhibition of RNA translation may be an important component of the antitumor effects of phenethyl isothiocyanate...
  30. doi request reprint Differing effects of rapamycin and mTOR kinase inhibitors on protein synthesis
    Yilin Huo
    School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK
    Biochem Soc Trans 39:446-50. 2011
    ..Synthesis of proteins encoded by 'non-TOP' mRNAs was less inhibited by mTOR kinase inhibitors and especially by rapamycin. The implications of our findings are discussed...
  31. ncbi request reprint Analysis of the subunit organization of the eIF2B complex reveals new insights into its structure and regulation
    Noel C Wortham
    1University of Southampton, Centre for Biological Sciences Life Sciences Building 85, Highfield Campus, Southampton SO17 1BJ, UK
    FASEB J 28:2225-37. 2014
    ..Wortham, N. C., Martinez, M., Gordiyenko, Y., Robinson, C. V., Proud, C. G. Analysis of the subunit organization of the eIF2B complex reveals new insights into its structure and regulation. ..
  32. pmc mTOR's role in ageing: protein synthesis or autophagy?
    Sarah L Hands
    School of Biological Sciences, University of Southampton, Southampton, Boldrewood Campus, Basset Crescent East, SO16 7PX, UK
    Aging (Albany NY) 1:586-97. 2009
    ..In this article we discuss the relative importance of both these processes in ageing, identify how TOR regulates translation and autophagy and speculate on links between the TOR signaling network and ageing pathways...
  33. ncbi request reprint Signalling to translation: how signal transduction pathways control the protein synthetic machinery
    Christopher G Proud
    Department of Biochemistry and Molecular Biology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3
    Biochem J 403:217-34. 2007
    ..However, important questions remain about both the contributions of individual regulatory events to the control of general protein synthesis and the mechanisms by which the translation of specific mRNAs is controlled...
  34. doi request reprint The eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation
    Gabriel Leprivier
    Department of Molecular Oncology, British Columbia Cancer Research Centre, University of British Columbia UBC, Vancouver, BC V5Z1L4, Canada
    Cell 153:1064-79. 2013
    ..Our data highlight a conserved role for eEF2K in protecting cells from nutrient deprivation and in conferring tumor cell adaptation to metabolic stress. PAPERCLIP:..
  35. doi request reprint Severity of vanishing white matter disease does not correlate with deficits in eIF2B activity or the integrity of eIF2B complexes
    Rui Liu
    Department of Biochemistry, School of Life Sciences, Fudan University, Shanghai, People s Republic of China
    Hum Mutat 32:1036-45. 2011
    ....
  36. ncbi request reprint Eukaryotic elongation factor 2 kinase, an unusual enzyme with multiple roles
    Justin W Kenney
    Centre for Biological Sciences, Life Sciences Building, University of Southampton, Southampton, SO16 7LB, UK
    Adv Biol Regul 55:15-27. 2014
    ..Growing evidence points to roles for eEF2K in neurological processes such as learning and memory and perhaps in depression. ..
  37. doi request reprint Nutrient control of TORC1, a cell-cycle regulator
    Xuemin Wang
    School of Biological Sciences, University of Southampton, Southampton, UK
    Trends Cell Biol 19:260-7. 2009
    ..mTORC1 is known to control the G1/S transition of the cell cycle: new data show that (m)TORC1 also controls G2/M progression in yeast and mammals, albeit in contrasting ways...
  38. pmc Identification of residues that underpin interactions within the eukaryotic initiation factor (eIF2) 2B complex
    Xuemin Wang
    Centre for Biological Sciences, Life Sciences Building, University of Southampton, Southampton SO17 1BJ, United Kingdom
    J Biol Chem 287:8263-74. 2012
    ..Lastly, our data show that eIF2Bγ promotes the expression of eIF2Bε, providing a mechanism for achieving correct stoichiometry of these eIF2B subunits in the cell...
  39. ncbi request reprint A conserved loop in the catalytic domain of eukaryotic elongation factor 2 kinase plays a key role in its substrate specificity
    Claire E Moore
    Centre for Biological Sciences, Highfield Campus, University of Southampton, Southampton, United Kingdom
    Mol Cell Biol 34:2294-307. 2014
    ..This is similar to the situation for MHCK A and is consistent with this being a common feature of α-kinases. ..
  40. doi request reprint Oxidized LDL-mediated macrophage survival involves elongation factor-2 kinase
    Johnny H Chen
    Department of Medicine, University of British Columbia, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada
    Arterioscler Thromb Vasc Biol 29:92-8. 2009
    ..In this report, we investigate the mechanism of oxLDL-mediated macrophage survival...
  41. ncbi request reprint The mTOR pathway in the control of protein synthesis
    Xuemin Wang
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada
    Physiology (Bethesda) 21:362-9. 2006
    ..mTOR plays key roles in cell physiology. mTOR regulates numerous components involved in protein synthesis, including initiation and elongation factors, and the biogenesis of ribosomes themselves...
  42. ncbi request reprint Protein kinase D is a key regulator of cardiomyocyte lipoprotein lipase secretion after diabetes
    Min Suk Kim
    Faculty of Pharmaceutical Sciences, Vancouver, BC, Canada
    Circ Res 103:252-60. 2008
    ..Results from this study could help in restricting cardiac LPL translocation, leading to strategies that overcome contractile dysfunction after diabetes...
  43. pmc A sharper instrument for dissecting signalling events: a specific AGC kinase inhibitor
    Christopher G Proud
    Department of Biochemistry and Molecular Biology, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3
    Biochem J 401:e1-3. 2007
    ....
  44. ncbi request reprint Crosstalk between mTOR complexes
    Jianling Xie
    Centre for Biological Sciences, Life Sciences Building B85, University of Southampton, Southampton SO17 1BJ, UK
    Nat Cell Biol 15:1263-5. 2013
    ..The two complexes are now shown to be involved in a negative feedback regulatory mechanism, in which mTORC1 stimulation inactivates mTORC2 through the inhibitory phosphorylation of the mTORC2 component Sin1. ..