|dc.description.abstract||Aurora B kinase, the enzymatic subunit of the chromosomal passenger complex, plays a pivotal role in the regulation of chromosome segregation and cytokinesis. Therefore, Aurora B activity is tightly regulated through modulating (1) gene expression, (2) activation, (3) localization and (4) degradation of Aurora B, and by (5) dephosphorylation of its substrates. Deregulation of Aurora B might play a role in cancer, since changes in Aurora B activity cause chromosome segregation errors and cytokinesis failure leading to aneuploidy, which is a hallmark of cancer. This thesis describes the regulation of Aurora B activity and reviews the evidence regarding a causal role for deregulation of Aurora B activity in tumors.
Heterozygous Aurora B knock-out mice are more prone to cancer development. Conversely, Aurora B mRNA and protein levels are frequently upregulated in human tumors. Indirect evidence which suggests that upregulation of Aurora B might contribute to tumor malignancy can however not be extrapolated to humans, and therefore a causal role for Aurora B upregulation in tumor development has not been established yet. Furthermore, the evidence regarding deregulation of Aurora B in human cancer is incomplete. For instance, it is still largely unknown whether the upregulation of Aurora B in cancer is caused by an increase in gene expression, a decrease in degradation or both. Additionally, the influence of deregulating Aurora B activity without changing Aurora B protein levels on tumor development is undetermined. Research should focus on unraveling these mentioned aspects regarding the link between deregulated Aurora B activity and tumor development. For now, the role of deregulated Aurora B activity in human cancer remains unclear.||