Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/162047
Title: | Phosphofructokinases Axis Controls Glucose-Dependent mTORC1 Activation Driven by E2F1. |
Author: | Almacellas i Canals, Eugènia Pelletier, Joffrey Manzano Cuesta, Anna Gentilella, Antonio Ambrosio Viale, Santiago Mauvezin, Caroline Tauler Girona, Albert |
Keywords: | Cèl·lules canceroses Glucosa Glucòlisi Lisosomes Cancer cells Glucose Glycolysis Lysosomes |
Issue Date: | 25-Oct-2019 |
Publisher: | Elsevier |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1016/j.isci.2019.09.040 |
It is part of: | iScience, 2019, vol. 20, p. 434-448 |
URI: | http://hdl.handle.net/2445/162047 |
Related resource: | https://doi.org/10.1016/j.isci.2019.09.040 |
ISSN: | 2589-0042 |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Fisiologia) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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