**2.2. Aurora-B**

three domains: a N-terminal domain with little similarity among the three Aurora kinases, instrumental in determining their different intracellular localizations, substrate specificity and functions; a catalytic domain, containing the activation loop and highly related in sequence among the three proteins; and a short C-terminal domain of 15–20 residues (**Figure 1**). Aurora kinase expression is tightly regulated during cell cycle, being low in the G1/S phase and

**Figure 1.** Schematic representation of Aurora kinase proteins. D-Box, destruction box; DAD, D box activating domain; KEN motif, amino acidic K-E-N, which serves as targeting signal for the Cdh1–anaphase promoting complex (adapted

The Aurora-A is encoded by the *AURKA* gene located on the chromosome 20q13.2 and containing 11 exons (Gene ID: 6790). The *AURKA* promoter contains a putative TATA box at −37 to −14 and two CCAAT boxes at −101 to −88 and at −69 to −56 [Eukaryotic Promoter Database, Swiss Institute of Bioinformatics]. Two distinct cis-regulatory elements have been identified [40]. Of these, one positively regulates *AURKA* gene transcription, while the other is a cell cycle-dependent transcriptional repressor [40]. The former, essential for the gene expression, is a 7-bp sequence located at −85 to −79 that binds the transcription factor E4TF1. The second is formed by two repressor elements: a cell cycle-dependent element (CDE) located at −44 to −40, and a cell cycle gene homology region (CHR) located at −39 to −35 [40]. Over the last few years, a number of transcription factors capable of repressing or inducing *AURKA* gene expression have been identified. These include the p53, the HIF-1, and the INI1/hSSNF5, all reported to regulate negatively the activity of the *AURKA* promoter [41–43]. Conversely, other transcription factors have been shown to induce *AURKA* expression, among which the ΔEGFR/STAT5, the oncogene MYCN, and the MAPK via Ets2 transcription factors [44–47]. The

maximal in the G2/M phase.

98 Anti-cancer Drugs - Nature, Synthesis and Cell

with permission from Ref. [14]).

**2.1. Aurora-A**

The Aurora-B is encoded by the *AURKB* gene mapped to chromosome 17p13.1, and consisting of nine exons (Gene ID: 9212). Its promoter contains three putative CAAT boxes at −99 to −86, at −66 to −53, and at −30 to −17 [Eukaryotic Promoter Database, Swiss Institute of Bioinformatics]. As above described for the *AURKA* promoter, also the *AURKB* promoter possesses the CDE and CHR elements, thought to be responsible for the regulation of gene expression throughout the cell cycle [54]. *AURKB* promoter activity is positively increased by transcription factors such the ETS2 *via* ETS-binding sites present in its sequence [46, 47]. The 1.4 kb transcript encodes a protein of 345 amino acids with a predicted molecular mass of 39 kDa (**Figure 1**) [39]. As Aurora-A, Aurora-B protein is characterized by a catalytic domain, a C-terminal D box, and an N-terminal A box/DAD [49–53]. However, different from Aurora-A, Aurora-B is not degraded by the same ubiquitin ligase, but following its binding to the human proteasome α-subunit C8 in a proteasome-dependent manner [55].
