The cellular geography of Aurora kinases

The Aurora family of conserved serine/threonine kinases perform essential functions during cell division. The three mammalian paralogues are very similar in sequence, but differ significantly in their localization, function, substrates and regulatory partners.Aurora A is mainly associated with the spindle poles during mitosis, where it is required for centrosome separation and maturation. Spindle assembly requires that targeting protein for XKLP 2 (TPX2) targets Aurora A to spindle pole microtubules through a mechanism that requires Ran–GTP. Aurora A also functions in meiosis, promoting oocyte maturation, polar-body extrusion, spindle positioning and exit from metaphase I.Regulation of Aurora A occurs through phosphorylation/dephosphorylation and degradation. Protein phosphatase 1 negatively regulates Aurora and this interaction is modulated by TPX2. The Cdh1/Fizzy-related form of anaphase-promoting complex/cyclosome (APC/C) targets Aurora for degradation in late mitosis.Aurora B is a chromosomal-passenger protein with multiple functions in mitosis. Inner centromere protein (INCENP) and survivin, two other components of the passenger complex, function as targeting and regulatory factors for the kinase. Aurora B is required for phosphorylation of histone 3, targeting of condensin and normal chromosome compaction. It has also been recently shown to be essential for chromosome biorentation, kinetochore–microtubule interactions and the spindle-assembly checkpoint.Aurora B is essential for completion of cytokinesis. Myosin II regulatory chain, vimentin, desmin and glial fibrillary acidic protein are among its cleavage furrow substrates. Aurora B phosphorylates MgcRacGAP transforming it into an activator of RhoA in the contractile ring.Much less is known about Aurora-C kinases, other than that they seem to be preferentially expressed in meiotic cells — they are not discussed here in detail.Misexpression of Aurora kinases is linked to cancer, but their possible role in carcinogenesis is yet to be elucidated.During the cell cycle, Aurora kinases travel to their subcellular targets aided by their binding partner-substrates, INCENP, survivin and TPX2. This provides an additional level of regulation that might be essential for the choreography of mitotic events.