TY - JOUR
T1 - Aurora-C kinase supports mitotic progression in the absence of Aurora-B
AU - Slattery, Scott D.
AU - Mancini, Michael A.
AU - Brinkley, Bill R.
AU - Hall, Rebecca M.
N1 - Funding Information:
We thank Adam Szafran for initial support in the development of image analysis tools, Subrata Sen for reagents, Ivan Uray and Thuy-Ai Nguyen for technical assistance, and Denae Nash, Mei Leng, Ralph Dittman, Shelley Sazer, Lynn Zecheidrich, Sharon Dent and Li-Yuan Yu-Lee for discussions. This work was funded by a grant from the Huffington Foundation (to B.R.B. and R.M.H.) and in part from a pilot grant from the Dan L. Duncan Cancer Center (to L.Yu-L. and B.R.B.). Imaging resources were supported by U54 HD-07495 (O’Malley), P30 CA125123 (Osborne), P30 DK56338 (Estes), the Dan L. Duncan Cancer Center and the John S. Dunn Gulf Coast Consortium for Chemical Genomics. The authors thank Jeff Price (Vala Sciences, www.valasciences.com) and Tim Moran (www.accelrys.com) for long-standing high throughput microscopy and image analysis support, and technical support.
PY - 2009/9/15
Y1 - 2009/9/15
N2 - 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.
AB - 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.
KW - Aurora-B
KW - Aurora-C
KW - Chromosome congression
KW - High content analysis
KW - High throughput microscopy
KW - Mitosis
KW - Spindle assembly checkpoint
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U2 - 10.4161/cc.8.18.9591
DO - 10.4161/cc.8.18.9591
M3 - Article
C2 - 19713763
AN - SCOPUS:70349292180
SN - 1538-4101
VL - 8
SP - 2986
EP - 2997
JO - Cell Cycle
JF - Cell Cycle
IS - 18
ER -