title: Nuclear localization of γ-tubulin affects E2F transcriptional activity and S-phase progression.
abstract: We show that the centrosome- and microtubule-regulating protein γ-tubulin interacts with E2 promoter binding factors (E2Fs) to modulate E2F transcriptional activity and thereby control cell cycle progression. γ-Tubulin contains a C-terminal signal that results in its translocation to the nucleus during late G(1) to early S phase. γ-Tubulin mutants showed that the C terminus interacts with the transcription factor E2F1 and that the E2F1-γ-tubulin complex is formed during the G(1)/S transition, when E2F1 is transcriptionally active. Furthermore, E2F transcriptional activity is altered by reduced expression of γ-tubulin or by complex formation between γ-tubulin and E2F1, E2F2, or E2F3, but not E2F6. In addition, the γ-tubulin C terminus encodes a DNA-binding domain that interacts with E2F-regulated promoters, resulting in γ-tubulin-mediated transient activation of E2Fs. Thus, we report a novel mechanism regulating the activity of E2Fs, which can help explain how these proteins affect cell cycle progression in mammalian cells.
authors.affiliation: Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, Skåne University Hospital, Malmö, Sweden.
authors.forename: Greta
authors.initials: G
authors.lastname: Höög
authors.forename: Reihaneh
authors.initials: R
authors.lastname: Zarrizi
authors.forename: Kristoffer
authors.initials: K
authors.lastname: von Stedingk
authors.forename: Kristina
authors.initials: K
authors.lastname: Jonsson
authors.forename: Maria
authors.initials: M
authors.lastname: Alvarado-Kristensson
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism; D050684:E2F Transcription Factors / Q000378:metabolism*; D050687:E2F1 Transcription Factor / Q000378:metabolism*; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D019913:Nuclear Localization Signals / Q000502:physiology*; D012516:Osteosarcoma / Q000378:metabolism; D016196:S Phase / Q000502:physiology*; D015533:Transcriptional Activation; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D019913:Nuclear Localization Signals; D014404:Tubulin