Nuclear localization of γ-tubulin affects E2F transcriptional activity and S-phase progression

We show that the centrosome- and microtubule-regulating protein gamma-tubulin interacts with E2 promoter binding factors (E2Fs) to modulate E2F transcriptional activity and thereby control cell cycle progression. gamma-Tubulin contains a C-terminal signal that results in its translocation to the nucleus during late G(1) to early S phase. gamma-Tubulin mutants showed that the C terminus interacts with the transcription factor E2F1 and that the E2F1-gamma-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 gamma-tubulin or by complex formation between gamma-tubulin and E2F1, E2F2, or E2F3, but not E2F6. In addition, the gamma-tubulin C terminus encodes a DNA-binding domain that interacts with E2F-regulated promoters, resulting in gamma-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.-Hoog, G., Zarrizi, R., von Stedingk, K., Jonsson, K., Alvarado-Kristensson, M. Nuclear localization of gamma-tubulin affects E2F transcriptional activity and S-phase progression. FASEB J. 25, 3815-3827 (2011). www.fasebj.org