Late mitotic functions of Aurora kinases

Abstract

The coordination between late mitotic events such as poleward chromosome motion, spindle elongation, DNA decondensation, and nuclear envelope reformation (NER) is crucial for the completion of chromosome segregation at the anaphase-telophase transition. Mitotic exit is driven by a decrease of Cdk1 kinase activity and an increase of PP1/PP2A phosphatase activities. More recently, Aurora kinases have also emerged as master regulators of late mitotic events and cytokinesis. Aurora A is mainly associated with spindle poles throughout mitosis and midbody during telophase, whereas Aurora B re-localizes from centromeres in early mitosis to the spindle midzone and midbody as cells progress from anaphase to the completion of cytokinesis. Functional studies, together with the identification of a phosphorylation gradient during anaphase, established Aurora B as a major player in the organization of the spindle midzone and in the spatiotemporal coordination between chromosome segregation and NER. Aurora A has been less explored, but a cooperative role in spindle midzone stability has also been proposed, implying that both Aurora A and B contribute to accurate chromosome segregation during mitotic exit. Here, we review the roles of the Aurora kinases in the regulation of late mitotic events and discuss how they work together with other mitotic players to ensure an error-free mitosis.

AURKA destruction is decoupled from its activity at mitotic exit but suppresses interphase activity

“…AURKA activity increases in preparation for mitosis in parallel with the protein level, and both progressively drop from anaphase onwards. This has led to the expectation that destruction contributes to regulating AURKA activity at mitotic exit [28,33]. We observed, however, that loss of AURKA activity proceeds faster than destruction of the protein.…”

“…Although AURKA activity has been described to peak in M phase there has been no detailed characterization of how AURKA activity varies through mitosis. In particular the question of how AURKA activity is regulated during mitotic exit, given that AURKA also has anaphase functions [32,33], and the importance of its ongoing destruction for attenuation of activity, remain unresolved. We first used a commercially available antibody against the activated T-loop of Aurora kinases (pT288 in AURKA) that confirms by immunoblot the peak of active AURKA at mitosis in extracts from synchronised U2OS cells ( Figure 1A).…”

Single-Cell Dynamic Analysis of Mitosis in Haploid Embryonic Stem Cells Shows the Prolonged Metaphase and Its Association with Self-diploidization

“…It is also required for correct chromosome alignment and segregation during metaphase, and therefore regulates kinetochore functions (Afonso et al., 2016, Cheng et al., 2011, Lampson and Cheeseman, 2011). In addition, Aurora B plays critical roles in spindle checkpoint and cytokinesis (Ruchaud et al., 2007, Steigemann et al., 2008).…”

Phosphoproteome dynamics during mitotic exit in budding yeast

“…The budding yeast Polo-like kinase Cdc5 is essential for mitotic entry, chromosome segregation, and cytokinesis (Botchkarev & Haber, 2017). The Aurora kinase Ipl1 in turn is an integral part of the mitotic chromosome biorientation and segregation mechanism, with additional functions in the control of cytokinesis in higher eukaryotes (Afonso et al, 2017). Polo and Aurora kinases recognize (D/E/N)x (S/T) and (K/R)(K/R)x(S/T) motifs, respectively (Mok et al, 2010;Alexander et al, 2011).…”