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Plotnikova OV , Nikonova AS , Loskutov YV , Kozyulina PY , Pugacheva EN , Golemis EA
Calmodulin activation of Aurora-A kinase (AURKA) is required during ciliary disassembly and in mitosis
Mol Biol Cell. 2012 Jul;23(14) :2658-70
PMID: 22621899 PMCID: PMC3395655
AbstractThe centrosomal Aurora-A kinase (AURKA) regulates mitotic progression, and overexpression and hyperactivation of AURKA commonly promotes genomic instability in many tumors. Although most studies of AURKA focus on its role in mitosis, some recent work identified unexpected nonmitotic activities of AURKA. Among these, a role for basal body-localized AURKA in regulating ciliary disassembly in interphase cells has highlighted a role in regulating cellular responsiveness to growth factors and mechanical cues. The mechanism of AURKA activation involves interactions with multiple partner proteins and is not well understood, particularly in interphase cells. We show here that AURKA activation at the basal body in ciliary disassembly requires interactions with Ca(2+) and calmodulin (CaM) and that Ca(2+)/CaM are important mediators of the ciliary disassembly process. We also show that Ca(2+)/CaM binding is required for AURKA activation in mitosis and that inhibition of CaM activity reduces interaction between AURKA and its activator, NEDD9. Finally, mutated derivatives of AURKA impaired for CaM binding and/or CaM-dependent activation cause defects in mitotic progression, cytokinesis, and ciliary resorption. These results define Ca(2+)/CaM as important regulators of AURKA activation in mitotic and nonmitotic signaling.
NotesPlotnikova, Olga V Nikonova, Anna S Loskutov, Yuri V Kozyulina, Polina Y Pugacheva, Elena N Golemis, Erica A CA06927/CA/NCI NIH HHS/United States R01 CA063366/CA/NCI NIH HHS/United States R01 CA148671/CA/NCI NIH HHS/United States R01 CA63366/CA/NCI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Molecular biology of the cell Mol Biol Cell. 2012 Jul;23(14):2658-70. doi: 10.1091/mbc.E11-12-1056. Epub 2012 May 23.