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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Autores principales:	Sebastian Real, Nathalie Meo-Evoli, Lilia Espada, Albert Tauler
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3d027ccf9f644fbcb2fd354895d61cc4
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spelling	oai:doaj.org-article:3d027ccf9f644fbcb2fd354895d61cc42021-11-18T07:00:03ZE2F1 regulates cellular growth by mTORC1 signaling.1932-620310.1371/journal.pone.0016163https://doaj.org/article/3d027ccf9f644fbcb2fd354895d61cc42011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21283628/?tool=EBIhttps://doaj.org/toc/1932-6203During 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.Sebastian RealNathalie Meo-EvoliLilia EspadaAlbert TaulerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 1, p e16163 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sebastian Real Nathalie Meo-Evoli Lilia Espada Albert Tauler E2F1 regulates cellular growth by mTORC1 signaling.
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.
format	article
author	Sebastian Real Nathalie Meo-Evoli Lilia Espada Albert Tauler
author_facet	Sebastian Real Nathalie Meo-Evoli Lilia Espada Albert Tauler
author_sort	Sebastian Real
title	E2F1 regulates cellular growth by mTORC1 signaling.
title_short	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_sort	e2f1 regulates cellular growth by mtorc1 signaling.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/3d027ccf9f644fbcb2fd354895d61cc4
work_keys_str_mv	AT sebastianreal e2f1regulatescellulargrowthbymtorc1signaling AT nathaliemeoevoli e2f1regulatescellulargrowthbymtorc1signaling AT liliaespada e2f1regulatescellulargrowthbymtorc1signaling AT alberttauler e2f1regulatescellulargrowthbymtorc1signaling
_version_	1718424096204652544

E2F1 regulates cellular growth by mTORC1 signaling.

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