Aurora kinases are an important class of serine/threonine kinases responsible for regulating cell mitosis. In different model organisms, the structure and function of each family member of Aurora kinase are highly conserved. In recent years, with the continuous deepening of related research on aurora kinases, people have gradually realized the important functions of aurora kinases in cell mitosis and tumor formation. In cell mitosis, aurora kinases are involved in multiple events such as centrosome maturation and separation, spindle assembly and maintenance, chromosome separation, and cytokinesis. Abnormally expressed aurora kinases often cause a large number of abnormalities in cells during mitosis. In addition, aurora kinases are also involved in the process of tumor formation. It has been found that some small molecules that target deaurora have significant antitumor effects.

Introductions

To date, three Aurora kinases have been identified in mammalian cells. In addition to being considered as mitotic regulators, these three kinases have attracted great interest in the field of cancer research due to their elevated expression profiles in many human cancers. The human Aurora kinase has a similar domain structure, with an N-terminal domain of 39–129 residues in length, a related Ser/Thr protein kinase domain and a shorter C-terminal domain, which contains 15-20 Residues. The N-terminal domains of the three proteins share low sequence conservation, which determines the selectivity of protein-protein interactions.

Aurora kinase family

The human genome contains three members of the Aurora kinase family: Aurora A kinase, Aurora B kinase, and Aurora C kinase. In all studied species, the three Aurora mitotic kinases are located in the centrosome at different stages of mitosis. Conserved C-terminal catalytic domain. However, their N-terminal domains show large differences in size and sequence. Aurora A and Aurora B kinases play an important role in mitosis. Aurora A kinase is involved in centrosome maturation and isolation, thereby regulating spindle assembly and stability. Aurora B kinase is a chromosomal passenger protein that regulates chromosome segregation and cytokinesis. Although there is evidence that Aurora C may be a chromosomal passenger protein, its cellular function is unknown.

Aurora A kinase

Aurora kinase A, also known as serine/threonine protein kinase 6, is an enzyme encoded by the AURKA gene in humans. Aurora A is a member of the mitotic serine/threonine kinase family. It is related to important processes in mitosis and meiosis, and its normal function is necessary for healthy cell proliferation. Aurora A is activated by one or more phosphorylation and its activity peaks during the G2 to M phase transition of the cell cycle.

Figure 1. Protein structure of Aurora kinase A.

Clinical significance

Aurora A disorders are associated with a high incidence of cancer. For example, one study showed that Aurora A was overexpressed in 94% of invasive tissue growth in breast cancer, while Aurora A expression was normal in surrounding healthy tissue. Aurora A has also been shown to be involved in epithelial-mesenchymal transition and neuroendocrine transdifferentiation of prostate cancer cells in aggressive diseases. Aurora A disorders can cause cancer because Aurora A is required to complete cytokinesis. If a cell starts mitosis and replicates its DNA, but then fails to divide into two separate cells, it will become aneuploid, containing more chromosomes than normal chromosomes. Aneuploidy is a feature of many cancerous tumors. Usually, the expression level of Aurora A is controlled by the tumor suppressor protein p53.

Aurora B kinase

Aurora B kinase is a protein that plays a role in the attachment of mitotic spindles to centromeres. Chromosome segregation during mitosis and meiosis is regulated by kinases and phosphatases. Aurora kinases bind to microtubules during chromosome movement and separation. Aurora kinase B is localized to microtubules near animals and plants, especially special microtubules called K fibers, while Aurora kinase A is localized to the centrosome.

Reference:

1. Sen S; et al. A putative serine/threonine kinase encoding gene BTAK on chromosome 20q13 is amplified and overexpressed in human breast cancer cell lines. Oncogene. 1997, 14 (18): 2195–200.