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

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. FASEB J. 25, 3815–3827 (2011). www.fasebj.org