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E2F1 Regulates Cellular Growth by mTORC1 Signaling

During cell proliferation, growth must occur to maintain homeostatic cell size. Here we show that E2F1 is capable of inducing growth by regulating mTORC1 activity. The activation of cell growth and mTORC1 by E2F1 is dependent on both E2F1's ability to bind DNA and to regulate gene transcription...

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Detalles Bibliográficos
Autores principales: Real, Sebastian, Meo-Evoli, Nathalie, Espada, Lilia, Tauler, Albert
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3026008/
https://www.ncbi.nlm.nih.gov/pubmed/21283628
http://dx.doi.org/10.1371/journal.pone.0016163
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author Real, Sebastian
Meo-Evoli, Nathalie
Espada, Lilia
Tauler, Albert
author_facet Real, Sebastian
Meo-Evoli, Nathalie
Espada, Lilia
Tauler, Albert
author_sort Real, Sebastian
collection PubMed
description During cell proliferation, growth must occur to maintain homeostatic cell size. Here we show that E2F1 is capable of inducing growth by regulating mTORC1 activity. The activation of cell growth and mTORC1 by E2F1 is dependent on both E2F1's ability to bind DNA and to regulate gene transcription, demonstrating that a gene induction expression program is required in this process. Unlike E2F1, E2F3 is unable to activate mTORC1, suggesting that growth activity could be restricted to individual E2F members. The effect of E2F1 on the activation of mTORC1 does not depend on Akt. Furthermore, over-expression of TSC2 does not interfere with the effect of E2F1, indicating that the E2F1-induced signal pathway can compensate for the inhibitory effect of TSC2 on Rheb. Immunolocalization studies demonstrate that E2F1 induces the translocation of mTORC1 to the late endosome vesicles, in a mechanism dependent of leucine. E2F1 and leucine, or insulin, together affect the activation of S6K stronger than alone suggesting that they are complementary in activating the signal pathway. From these studies, E2F1 emerges as a key protein that integrates cell division and growth, both of which are essential for cell proliferation.
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spelling pubmed-30260082011-01-31 E2F1 Regulates Cellular Growth by mTORC1 Signaling Real, Sebastian Meo-Evoli, Nathalie Espada, Lilia Tauler, Albert PLoS One Research Article During cell proliferation, growth must occur to maintain homeostatic cell size. Here we show that E2F1 is capable of inducing growth by regulating mTORC1 activity. The activation of cell growth and mTORC1 by E2F1 is dependent on both E2F1's ability to bind DNA and to regulate gene transcription, demonstrating that a gene induction expression program is required in this process. Unlike E2F1, E2F3 is unable to activate mTORC1, suggesting that growth activity could be restricted to individual E2F members. The effect of E2F1 on the activation of mTORC1 does not depend on Akt. Furthermore, over-expression of TSC2 does not interfere with the effect of E2F1, indicating that the E2F1-induced signal pathway can compensate for the inhibitory effect of TSC2 on Rheb. Immunolocalization studies demonstrate that E2F1 induces the translocation of mTORC1 to the late endosome vesicles, in a mechanism dependent of leucine. E2F1 and leucine, or insulin, together affect the activation of S6K stronger than alone suggesting that they are complementary in activating the signal pathway. From these studies, E2F1 emerges as a key protein that integrates cell division and growth, both of which are essential for cell proliferation. Public Library of Science 2011-01-24 /pmc/articles/PMC3026008/ /pubmed/21283628 http://dx.doi.org/10.1371/journal.pone.0016163 Text en Real et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Real, Sebastian
Meo-Evoli, Nathalie
Espada, Lilia
Tauler, Albert
E2F1 Regulates Cellular Growth by mTORC1 Signaling
title E2F1 Regulates Cellular Growth by mTORC1 Signaling
title_full E2F1 Regulates Cellular Growth by mTORC1 Signaling
title_fullStr E2F1 Regulates Cellular Growth by mTORC1 Signaling
title_full_unstemmed E2F1 Regulates Cellular Growth by mTORC1 Signaling
title_short E2F1 Regulates Cellular Growth by mTORC1 Signaling
title_sort e2f1 regulates cellular growth by mtorc1 signaling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3026008/
https://www.ncbi.nlm.nih.gov/pubmed/21283628
http://dx.doi.org/10.1371/journal.pone.0016163
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