Mitotic mechanics: the auroras come into view

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Abstract

Aurora kinases have recently taken centre stage in the regulation of key cell cycle processes. Aurora A is emerging as a critical regulator of centrosome and spindle function. Aurora B mediates chromosome segregation by ensuring proper biorientation of sister chromatids, possibly through the regulation of microtubule dynamics. This enzyme also functions in cytokinesis apparently by interacting with a critical GTPase and a kinesin-like protein. Recent work on both kinases has revealed functional links between Aurora kinase activity and the mechanics of cell division.

Introduction

The Aurora protein kinases are currently one of the most intensely studied families of protein kinases. In vertebrates, they comprise Aurora A, Aurora B and Aurora C, with one or more highly conserved orthologues being found in the yeasts, flies, worms and other invertebrates. Their regulator influence spans from G2 through to cytokinesis, encompassing key cell-cycle events such as centrosome duplication, chromosome bi-orientation and segregation and cleavage-furrow positioning and ingression. Their localisation at critical points in the cell cycle is tightly coupled to their activity and function. In this review, we mainly focus on the functions of Aurora A and B, as they have received much attention over the past few years. We discuss the progress made in unravelling the functions of these kinases within the cell division cycle and the identity of critical downstream effectors and consider the ways in which these kinases are regulated within cells.

Section snippets

Aurora A and spindle formation

Aurora A is localized at the spindle poles from prophase through to telophase (see Figure 1a) and has emerged as a critical factor in the assembly of the mitotic spindle in metazoans. Depletion of Aurora A by RNA-mediated interference (RNAi) disrupts centrosomal recruitment of γ-tubulin in Caenorhabditis elegans [1] and D-TACC, centrosomin and γ-tubulin in Drosophila 2., 3., leading to various defects in microtubule and centrosome morphology during mitosis in these animals 1., 2.. D-TACC, which

Aurora B

Aurora B is a chromosome passenger protein, localising on centromeres from prophase through to the metaphase–anaphase transition. It then relocalises in anaphase to the spindle midzone and cortex at the site of furrow ingression (see Figure 1a). Before anaphase, Aurora B is concentrated at the ‘inner centromere’, a chromatin-rich region between centromeres (See Figure 1b). The founding member of the chromosome passenger proteins is INCENP, which for many years was known to be involved in

Conclusions

The Aurora kinases represent a fascinating family of molecules whose activities impinge on a large number of critical cell functions. Their discovery has coincided with the development of many new technologies (RNAi, live cell imaging, etc.) that provide functional analyses in many different experimental systems. Experimental progress, especially with the Aurora B complex, has been rapid over the past two years and, if anything, the pace in this exciting field is increasing. These fascinating

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

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