Aurora-C kinase supports mitotic progression in the absence of Aurora-B

Abstract

Aurora family kinases regulate numerous mitotic processes, and their dysfunction or overexpression can cause aneuploidy, a contributing factor for tumorigenesis. In vertebrates, the Aurora-B kinase regulates kinetochore maturation, destabilization of improper kinetochore-microtubule attachments, the spindle assembly checkpoint, central spindle organization and cytokinesis. A gene duplication event created the related Aurora-C kinase in mammals. While Aurora-C function is unclear, it has similar structural and localization properties as Aurora-B. Inhibition of either Aurora-B or Aurora-C function causes aneuploidy, while simultaneous inhibition of both causes a higher frequency of aneuploidy. To determine if Aurora-C and -B have overlapping or unique complementary functions during mitosis, we created a system where Aurora-B is replaced by wild-type or kinase-defective mutant Aurora-C in HeLa cells. In this model, Aurora-B protein levels and mitotic functions were suppressed including the regulation of kinetochore-microtubule attachments, the spindle assembly checkpoint, and cytokinesis. Wild-type, but not kinase-defective Aurora-C expression, was able to rescue these functions. Therefore, Aurora-C can perform the same essential functions as Aurora-B in mitosis.