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

ABSTRACT: We show that the centrosome- and microtubule-regulating protein ?-tubulin interacts with E2 promoter binding factors (E2Fs) to modulate E2F transcriptional activity and thereby control cell cycle progression. ?-Tubulin contains a C-terminal signal that results in its translocation to the nucleus during late G(1) to early S phase. ?-Tubulin mutants showed that the C terminus interacts with the transcription factor E2F1 and that the E2F1-?-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 ?-tubulin or by complex formation between ?-tubulin and E2F1, E2F2, or E2F3, but not E2F6. In addition, the ?-tubulin C terminus encodes a DNA-binding domain that interacts with E2F-regulated promoters, resulting in ?-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.

SUBMITTER: Hoog G 

PROVIDER: S-EPMC3205837 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature