**3. Expression, subcellular localization, and functions of the Aurora kinases**

The Aurora kinases play a major role during mitosis [49, 50]. As mentioned above, these proteins display distinct intracellular localizations, substrate specificity and functions, and their expression and activity are tightly regulated at the transcriptional or posttranscriptional level, through phosphorylation/dephosphorylation and protein degradation [57].

## **3.1. Aurora-A**

The expression of Aurora-A is cell cycle regulated, being very low during the G1-phase and starting to accumulate at the centrosome in the late S phase to be maximal at the G2-M transition. In this period, it localizes at the spindle poles, and it is degraded before cytokinesis [50, 53]. Aurora-A regulates centrosome separation and maturation, mitotic entry, and bipolar spindle formation. Recruitment of Aurora-A to the centrosome is controlled by the centrosome

**Figure 2.** (A) Schematic representation of the pathway induced by Aurora-A to activate the CDK1/cyclin B complex allowing the transition of the cell from the G2 to the M phase. Aurora-A in association with Bora phosphorylates the PLK1. Both Aurora-A and PLK1 phosphorylate CDC25B (cell division cycle 25 B) allowing cyclin-dependent kinase 1 (CDK1)/cyclin B complex activation and thus promoting mitotic entry. PLK1 facilitates this process also by inhibiting the CDK1 inhibitor WEE1. Inactivation of Aurora-A or Plk1 individually shows no significant effect on Cdk1 activation and entry to mitosis, while their simultaneous inactivation produces a marked delay in both Cdk1 activation and mitotic entry, suggesting that the two kinases have redundant functions. (B) Immunofluorescence showing Aurora-A localization at the spindle pole of an anaplastic thyroid cancer cell in metaphase. Adapted with permission from Ref. [14].

protein of 192 kDa/spindle defective 2 (Cep192/Spd-2) [58]. On the centrosome, Aurora-A promotes the concentration in the pericentriolar mass of a number of proteins required for centrosome maturation and function. These include centrosomin, γ-tubulin, large tumor suppressor, homolog 2 (LATS2), transforming acidic coiled coil 3 (TACC3), and nuclear distribution element-like 1 (NDEL1) [50, 53, 59]. A central role of Aurora-A during mitosis is that to support the microtubule-organizer center (MTOC) responsible for the formation of the bipolar spindle. In this context, Aurora-A has been shown to form complexes with TACC1 and TACC3, which in turn, by binding to ch-TOG/XMAP215 proteins, stabilize microtubules at the centrosome [60–62]. In addition, Aurora-A interacts with and phosphorylates TPX2, which is capable of promoting spindle microtubule polymerization [53].

Aurora-A, along with the polo like kinase 1 (PLK1), controls the G2 to M phase transition (**Figure 2**) [63–65]. First, Aurora-A in association with the Bora protein phosphorylates the PLK1, after which both Aurora-A and PLK1 phosphorylate the cell division cycle 25 B (CDC25B), a member of the CDC25 family of phosphatases, which activates cyclin-dependent kinases by removing two phosphate groups, leading to CDK1/cyclin B complex activation and finally promoting mitotic entry [50, 63–66]. PLK1 facilitates this process also by inactivating the CDK1 inhibitor WEE1 (**Figure 2**).
