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Review
. 2021 Aug;147(8):2187-2198.
doi: 10.1007/s00432-021-03669-5. Epub 2021 May 28.

Aurora B kinase: a potential drug target for cancer therapy

Azaj Ahmed  1 , Anas Shamsi  1 , Taj Mohammad  1 , Gulam Mustafa Hasan  2 , Asimul Islam  1 , Md Imtaiyaz Hassan  3
Affiliations
Review

Aurora B kinase: a potential drug target for cancer therapy

Azaj Ahmed et al. J Cancer Res Clin Oncol. 2021 Aug.

Abstract

Background: Ensuring genetic integrity is essential during the cell cycle to avoid aneuploidy, one of the underlying causes of malignancies. Aurora kinases are serine/threonine kinase that play a vital role in maintaining the genomic integrity of the cells. There are three forms of aurora kinases in the mammalian cells, which are highly conserved and act together with several other proteins to control chromosome alignment and its equal distribution to daughter cells in mitosis and meiosis.

Methods: We provide here a detailed analysis of Aurora B kinase (ABK) in terms of its expression, structure, function, disease association and potential therapeutic implications.

Results: ABK plays an instrumental in mitotic entry, chromosome condensation, spindle assembly, cytokinesis, and abscission. Small-molecule inhibitors of ABK are designed and synthesized to control cancer progression. A detailed understanding of ABK pathophysiology in different cancers is of great significance in designing and developing effective therapeutic strategies.

Conclusion: In this review, we have discussed the physiological significance of ABK followed by its role in cancer progression. We further highlighted available small-molecule inhibitors to control the tumor proliferation and their mechanistic insights.

Keywords: Aneuploidy; Aurora kinase; Cancer therapeutics; Cell cycle regulation; Small molecule inhibitors.

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Conflict of interest statement

Authors declare no potential conflicts of interest.

Figures

Fig. 1
Fig. 1
Diagrammatical representation of all the three isoforms of Aurora kinases highlighting their different domains. All three auroras A, B, and C share homology in catalytic (shown in the green shade) and regulatory domain (grey shade). D-box is the destruction box tag for ubiquitin identification. KEN motif is present in Aurora A and B; it serves as a targeting signal for anaphase-promoting complex
Fig. 2
Fig. 2
Schematic representation of mitotic cell cycle events and highlighting the role of Aurora B kinase. The level of Aurora B kinase gets peaked in the M phase and remained high till cytokinesis
Fig. 3
Fig. 3
Showing the role of ABK in promoting malignancy. The overexpressed Aurora B kinase alters tumor suppressor gene (TSG) stability and induces different potential routes to trigger tumorigenesis (upper panel). The downregulation or inhibition of Aurora B kinase accelerates the TSG-regulated cell death and hinders the propensity of tumorigenesis (lower panel)
Fig. 4
Fig. 4
Alteration frequency and their types of ABK in different cancer types. Bar graph showing relative alteration frequency of ABK across the 300 studies of different cancer
See this image and copyright information in PMC

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