Abstract
Aurora kinases are serine/threonine kinases essential for the onset and progression of mitosis. Aurora members share a similar protein structure and kinase activity, but exhibit distinct cellular and subcellular localization. AurA favors the G2/M transition by promoting centrosome maturation and mitotic spindle assembly. AurB and AurC are chromosome-passenger complex proteins, crucial for chromosome binding to kinetochores and segregation of chromosomes. Cellular distribution of AurB is ubiquitous, while AurC expression is mainly restricted to meiotically-active germ cells. In human tumors, all Aurora kinase members play oncogenic roles related to their mitotic activity and promote cancer cell survival and proliferation. Furthermore, AurA plays tumor-promoting roles unrelated to mitosis, including tumor stemness, epithelial-to-mesenchymal transition and invasion. In this review, we aim to understand the functional interplay of Aurora kinases in various types of human cells, including tumor cells. The understanding of the functional diversity of Aurora kinases could help to evaluate their relevance as potential therapeutic targets in cancer.
Highlights
Aurora kinases are serine/threonine kinases essential for the onset and progression of mitosis
Mitosis In physiological conditions, mitosis is induced by activation of the Cyclin B1-CDK1 complex, which controls the transition of the G2/M checkpoint
Aurora A (AurA) loss induces monopolar spindles and aneuploidy, while Aurora B (AurB) deficiency alters chromosome distribution and cytokinesis resulting in bi-nucleated cells [9, 146]
Summary
Aurora kinases are serine/threonine kinases essential for the onset and progression of mitosis. Aurora members share a similar protein structure and kinase activity, but exhibit distinct cellular and subcellular localization. AurA favors the G2/M transition by promoting centrosome maturation and mitotic spindle assembly. All Aurora kinase members play oncogenic roles related to their mitotic activity and promote cancer cell survival and proliferation. We aim to understand the functional interplay of Aurora kinases in various types of human cells, including tumor cells. Needs to be rigorously regulated through efficient, timely and specific processes [3, 4] The majority of these regulators belongs to the mitotic kinome, which encompasses kinase families and their. Mitotic enzymes are usually degraded through the E3 ubiquitin ligase APC/C (anaphase promoting complex/cyclosome) at the end of mitosis [7, 8]
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