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Review
. 2015 Jan 29;34(5):537-45.
doi: 10.1038/onc.2014.14. Epub 2014 Mar 17.

The aurora kinases in cell cycle and leukemia

B Goldenson  1 , J D Crispino  1
Affiliations
Review

The aurora kinases in cell cycle and leukemia

B Goldenson et al. Oncogene. .

Abstract

The Aurora kinases, which include Aurora A (AURKA), Aurora B (AURKB) and Aurora C (AURKC), are serine/threonine kinases required for the control of mitosis (AURKA and AURKB) and meiosis (AURKC). Since their discovery nearly 20 years ago, Aurora kinases have been studied extensively in cell and cancer biology. Several early studies found that Aurora kinases are amplified and overexpressed at the transcript and protein level in various malignancies, including several types of leukemia. These discoveries and others provided a rationale for the development of small-molecule inhibitors of Aurora kinases as leukemia therapies. The first generation of Aurora kinase inhibitors did not fare well in clinical trials, owing to poor efficacy and high toxicity. However, the creation of second-generation, highly selective Aurora kinase inhibitors has increased the enthusiasm for targeting these proteins in leukemia. This review will describe the functions of each Aurora kinase, summarize their involvement in leukemia and discuss inhibitor development and efficacy in leukemia clinical trials.

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Conflict of interest statement

Conflicts of Interest

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1. Structure and domains of the aurora kinases
The Aurora kinases N-terminal and C-terminal domains contain D-box and KEN regulatory motifs while the central kinase domain contributes the catalytic activity. The central domain also includes key regulatory motifs such as the activation (T-loop) residue.
Figure 2
Figure 2. Aurora A and B are appropriately expressed and localized in mitosis
Aurora A localizes to the spindle poles, while Aurora B localizes to the midbody of the central spindle during mitosis. Triangles, Aurora A kinase; Circles, Aurora B kinase; L-shaped objects, centrosomes.
Figure 3
Figure 3. Aurora A and B are expressed and localized in endomitosis of megakaryocytes
Endomitotic cells are reported to show normal localization of both kinases , , . The major difference from the proliferative cell cycle is the regression of the cleavage furrow, which leads to polyploidy –. Triangles, Aurora A kinase; Circles, Aurora B kinase; L-shaped objects, centrosomes.
See this image and copyright information in PMC

References

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