Nuclear localization of {gamma}-tubulin affects E2F transcriptional activity and S-phase progression.

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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.-Höög, G., Zarrizi, R., von Stedingk, K., Jonsson, K., Alvarado-Kristensson, M. Nuclear localization of γ-tubulin affects E2F transcriptional activity and S-phase progression.

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  • Cell and Molecular Biology
Original languageEnglish
Pages (from-to)3815-3827
JournalFASEB Journal
Volume25
Issue number11
Publication statusPublished - 2011
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

Department affilation moved from v1000583 (Molecular Tumour Biology) to v1000562 (Department of Translational Medicine) on 2016-01-18 14:41:46.

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