title: E2F1 regulates cellular growth by mTORC1 signaling.
abstract: 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.
authors.affiliation: Departament de Bioquímica i Biologia Molecular, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Real
authors.forename: Nathalie
authors.initials: N
authors.lastname: Meo-Evoli
authors.forename: Lilia
authors.initials: L
authors.lastname: Espada
authors.forename: Albert
authors.initials: A
authors.lastname: Tauler
mesh_terms: D002453:Cell Cycle; D002455:Cell Division; D048708:Cell Growth Processes; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050687:E2F1 Transcription Factor / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007930:Leucine / Q000494:pharmacology; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases; D015533:Transcriptional Activation
chemical_list: D050687:E2F1 Transcription Factor; D007328:Insulin; D046912:Multiprotein Complexes; D011506:Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1; D007930:Leucine