Aurora-C kinase supports mitotic progression in the absence of Aurora-B.
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.
Slattery
Scott D
SD
Baylor College of Medicine, Department of Molecular and Cellular Biology, Houston, TX, USA.
Mancini
Michael A
MA
Brinkley
Bill R
BR
Hall
Rebecca M
RM
D064107:Aurora Kinase B; D064108:Aurora Kinase C; D064127:Aurora Kinases; D048749:Cytokinesis; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores; D008870:Microtubules; D008938:Mitosis; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000502:physiology*; D008941:Spindle Apparatus
C576921:AURKB protein, human; C576927:AURKC protein, human; D064107:Aurora Kinase B; D064108:Aurora Kinase C; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases