Abstract
The gene encoding the Aurora-A protein kinase is located in the 20q13 breast cancer amplicon and is also overexpressed in colorectal, pancreatic and gastric tumours. Although Aurora-A may not be a bona fide oncoprotein in humans, it is a promising drug target in cancer therapy. Thus, it is surprising that so little is known of its role in normal cells. The primary function of Aurora-A is to promote bipolar spindle assembly, but the molecular details of this process remained obscure until recently. The discovery of several novel Aurora-A-binding proteins and substrates has implicated Aurora-A in centrosome maturation and separation, acentrosomal and centrosomal spindle assembly, kinetochore function, cytokinesis and in cell fate determination. Here we discuss recent advances in determining the early mitotic role of Aurora-A, with a strong emphasis on its function at the mitotic spindle poles.
Highlights
Cell division is a highly complex process that has intrigued scientists for over a century
Whereas Aurora-B is required for chromosome bi-orientation and cytokinesis, Aurora-A has emerged as a major regulator of mitotic centrosomes and spindle assembly
In late G2 phase, the two centrosomes undergo maturation by recruiting additional pericentriolar matrix (PCM) components to prepare for their role as spindle poles
Summary
Cell division is a highly complex process that has intrigued scientists for over a century. Underneath the striking structural rearrangements lies a complex regulatory network of kinases and phosphatases that maintain the accuracy of cell division One such kinase is Aurora-A, a member of the evolutionary conserved Aurora serine/threonine kinase family. The rapid turnover of Aurora-A both in the centrosome and on the mitotic spindle argues for a signalling rather than a structural role for the kinase at these locations (Stenoien et al, 2003). This is not surprising, because as well as playing a significant role in organising the mitotic MT network, the centrosome acts as an important signalling platform (Azimzadeh and Bornens, 2007). The Aurora-A consensus phosphorylation site was defined in budding yeast as [KR]X[TS][ILV] (Cheeseman et al, 2002)
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