Chapter 10 - Aurora kinase: An emerging potential target in therapeutics

Abstract

Aurora kinases belong to the family of serine/threonine kinases that comprises Aurora kinase A (AURKA), Aurora kinase B (AURKB), and Aurora kinase C (AURKC). They play a crucial role in cell division by governing the process of mitosis. Aurora kinase family members share similar protein structures while having different cellular and subcellular localization, substrate specificity, and function during mitosis. AURKA and AURKB primarily control the process of mitosis, whereas AURKC has been mainly implicated in meiosis. AURKA elicited the transition from the G2/M phase by triggering the centrosome maturation and mitotic spindle assembly. On the other hand, AURKB, and AURKC are chromosome-passenger complex proteins that play key roles in chromosome binding to kinetochores and chromosomal segregation. Cellular distribution of AURKA and AURKB is ubiquitous, while AURKC expression is mainly restricted to meiotically-active germ cells. Dysfunction of these kinases has been correlated with the progression of different types of cancers. Several studies have demonstrated that the suppression of Aurora kinases could augment the effect of chemotherapies. Aurora kinase inhibitors have been prominently put into use, out of which few are presently being evaluated under ongoing clinical trials. These inhibitors have been reported to effectively inhibit the progression and growth in many of the cancers, both in-vitro and in-vivo. Thus, presenting Aurora kinases as a promising candidate to be used for therapeutic purposes. In this book chapter, we tried to briefly explain the different roles of Aurora kinases, their structure, cellular and subcellular localization. Further, we have described the oncogenic role of Aurora kinase in promoting tumorigenesis. The chapter also summarizes the various Aurora kinase inhibitors being investigated under preclinical and clinical studies and discusses the current and future directions.