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Almacellas E, Pelletier J, Manzano A, et al. Phosphofructokinases Axis Controls Glucose-Dependent mTORC1 Activation Driven by E2F1. iScience. 2019;20:434-448doi: 10.1016/j.isci.2019.09.040.
Almacellas, E., Pelletier, J., Manzano, A., Gentilella, A., Ambrosio, S., Mauvezin, C., & Tauler, A. (2019). Phosphofructokinases Axis Controls Glucose-Dependent mTORC1 Activation Driven by E2F1. iScience, 20434-448. https://doi.org/10.1016/j.isci.2019.09.040
Almacellas, Eugènia, et al. "Phosphofructokinases Axis Controls Glucose-Dependent mTORC1 Activation Driven by E2F1." iScience vol. 20 (2019): 434-448. doi: https://doi.org/10.1016/j.isci.2019.09.040
Almacellas E, Pelletier J, Manzano A, Gentilella A, Ambrosio S, Mauvezin C, Tauler A. Phosphofructokinases Axis Controls Glucose-Dependent mTORC1 Activation Driven by E2F1. iScience. 2019 Oct 25;20:434-448. doi: 10.1016/j.isci.2019.09.040. Epub 2019 Oct 01. PMID: 31627130; PMCID: PMC6818336.
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iScience. 2019 Oct 25;20:434-448. doi: 10.1016/j.isci.2019.09.040. Epub 2019 Oct 01.

Phosphofructokinases Axis Controls Glucose-Dependent mTORC1 Activation Driven by E2F1.

iScience

Eugènia Almacellas, Joffrey Pelletier, Anna Manzano, Antonio Gentilella, Santiago Ambrosio, Caroline Mauvezin, Albert Tauler

Affiliations

  1. Department of Biochemistry and Physiology, School of Pharmacy, University of Barcelona, Barcelona, Catalonia 08028, Spain; Laboratory of Cancer Metabolism, Molecular Mechanisms and Experimental Therapy in Oncology Program (Oncobell), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain.
  2. Laboratory of Cancer Metabolism, Molecular Mechanisms and Experimental Therapy in Oncology Program (Oncobell), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain.
  3. Biochemistry Unit, Physiological Sciences Department, Faculty of Medicine and Health Science, University of Barcelona (IDIBELL), Hospitalet del Llobregat, Barcelona, Catalonia 08907, Spain.
  4. Laboratory of Cancer Metabolism, Molecular Mechanisms and Experimental Therapy in Oncology Program (Oncobell), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain. Electronic address: [email protected].
  5. Department of Biochemistry and Physiology, School of Pharmacy, University of Barcelona, Barcelona, Catalonia 08028, Spain; Laboratory of Cancer Metabolism, Molecular Mechanisms and Experimental Therapy in Oncology Program (Oncobell), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain. Electronic address: [email protected].

PMID: 31627130 PMCID: PMC6818336 DOI: 10.1016/j.isci.2019.09.040

Abstract

Cancer cells rely on mTORC1 activity to coordinate mitogenic signaling with nutrients availability for growth. Based on the metabolic function of E2F1, we hypothesize that glucose catabolism driven by E2F1 could participate on mTORC1 activation. Here, we demonstrate that glucose potentiates E2F1-induced mTORC1 activation by promoting mTORC1 translocation to lysosomes, a process that occurs independently of AMPK activation. We showed that E2F1 regulates glucose metabolism by increasing aerobic glycolysis and identified the PFKFB3 regulatory enzyme as an E2F1-regulated gene important for mTORC1 activation. Furthermore, PFKFB3 and PFK1 were found associated to lysosomes and we demonstrated that modulation of PFKFB3 activity, either by substrate accessibility or expression, regulates the translocation of mTORC1 to lysosomes by direct interaction with Rag B and subsequent mTORC1 activity. Our results support a model whereby a glycolytic metabolon containing phosphofructokinases transiently interacts with the lysosome acting as a sensor platform for glucose catabolism toward mTORC1 activity.

Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

Keywords: Cell Biology; Molecular Genetics

References

  1. Gastroenterology. 2008 Oct;135(4):1322-32 - PubMed
  2. Cell Metab. 2016 Jan 12;23(1):27-47 - PubMed
  3. Oncogene. 1995 Oct 19;11(8):1509-17 - PubMed
  4. Mol Cell Biol. 2009 Jul;29(14):3991-4001 - PubMed
  5. Science. 2011 Nov 4;334(6056):678-83 - PubMed
  6. Endocrinology. 2003 Dec;144(12):5179-83 - PubMed
  7. Nat Cell Biol. 2011 Aug 14;13(9):1146-52 - PubMed
  8. Cell Metab. 2017 Aug 1;26(2):301-309 - PubMed
  9. Proc Natl Acad Sci U S A. 2009 Dec 22;106(51):21521-6 - PubMed
  10. J Biol Chem. 2003 May 30;278(22):20013-8 - PubMed
  11. Cancer Res. 2009 May 1;69(9):4052-8 - PubMed
  12. Genome Res. 2006 May;16(5):595-605 - PubMed
  13. Cell. 2006 Sep 8;126(5):955-68 - PubMed
  14. Cancer Res. 2013 Oct 1;73(19):6056-67 - PubMed
  15. Mol Cancer Ther. 2008 Jan;7(1):110-20 - PubMed
  16. Biochem Biophys Res Commun. 2008 Jan 11;365(2):291-7 - PubMed
  17. Nat Cell Biol. 2008 Aug;10(8):935-45 - PubMed
  18. Oncogene. 2008 Dec;27 Suppl 2:S43-51 - PubMed
  19. Cancer Epidemiol Biomarkers Prev. 2000 Apr;9(4):395-401 - PubMed
  20. J Cell Biol. 2017 Aug 7;216(8):2305-2313 - PubMed
  21. Eur J Biochem. 1982 Dec;129(1):191-5 - PubMed
  22. Sci Transl Med. 2012 Jun 20;4(139):139ra84 - PubMed
  23. Mol Cell. 2008 Apr 25;30(2):214-26 - PubMed
  24. Cancer Cell. 2007 Aug;12(2):108-13 - PubMed
  25. Front Oncol. 2018 Sep 04;8:331 - PubMed
  26. J Biol Chem. 1981 Apr 10;256(7):3171-4 - PubMed
  27. Oncogene. 2001 Mar 29;20(14):1678-87 - PubMed
  28. Mol Metab. 2019 Feb;20:1-13 - PubMed
  29. Cell Rep. 2015 Jul 7;12(1):102-115 - PubMed
  30. Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):11988-93 - PubMed
  31. Nat Commun. 2015 Dec 07;6:10028 - PubMed
  32. Cancer Cell. 2016 Sep 12;30(3):418-431 - PubMed
  33. Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):5992-7 - PubMed
  34. Oncogene. 2005 Jan 27;24(5):780-9 - PubMed
  35. IUBMB Life. 2010 Nov;62(11):791-6 - PubMed
  36. J Mol Cell Biol. 2013 Aug;5(4):214-26 - PubMed
  37. Nat Cell Biol. 2011 Apr;13(4):453-60 - PubMed
  38. Oncotarget. 2015 Sep 29;6(29):28057-70 - PubMed
  39. Nature. 2017 Aug 3;548(7665):112-116 - PubMed
  40. Nat Cell Biol. 2015 Oct;17(10):1304-16 - PubMed
  41. Cell. 2010 Apr 16;141(2):290-303 - PubMed
  42. Front Endocrinol (Lausanne). 2017 Nov 10;8:311 - PubMed
  43. Nat Cell Biol. 2002 Sep;4(9):648-57 - PubMed
  44. Cell. 2007 Jun 29;129(7):1261-74 - PubMed
  45. Cell. 2017 Apr 6;169(2):361-371 - PubMed
  46. Dev Cell. 2015 Apr 20;33(2):176-88 - PubMed
  47. Cell Metab. 2014 Sep 2;20(3):526-40 - PubMed
  48. Nat Rev Cancer. 2005 Nov;5(11):886-97 - PubMed
  49. Cell Cycle. 2005 Feb;4(2):310-4 - PubMed
  50. Cell Rep. 2016 Sep 13;16(11):3016-3027 - PubMed
  51. Cell. 2006 Jul 14;126(1):107-20 - PubMed
  52. Cell. 2012 Sep 14;150(6):1196-208 - PubMed
  53. Cell. 2005 Apr 22;121(2):179-93 - PubMed
  54. Gene. 1999 Mar 18;229(1-2):83-9 - PubMed
  55. J Cell Biol. 2017 Dec 4;216(12):4183-4197 - PubMed
  56. Sci Adv. 2015 Dec 18;1(11):e1500603 - PubMed
  57. PLoS One. 2011 Jan 24;6(1):e16163 - PubMed
  58. Oncotarget. 2015 May 10;6(13):11252-63 - PubMed
  59. Science. 1956 Feb 24;123(3191):309-14 - PubMed

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