Abstract
Aurora kinases are key cell cycle regulators and represent attractive new targets in cancer therapy. In this work we investigated the effect of specific inhibition of Aurora-A and Aurora-B on interphase microtubule dynamics using the GSK6000063A and AZD1152 HQPA compounds respectively. We show that Aurora-A inhibition results in microtubule network disorganization and bundling. Using video microscopy and laser-based photo ablation we demonstrate that Aurora-A inhibition decreases microtubule shrinkage, growth rate, frequency rescue and nucleation. These results open new perspectives on the role of Aurora-A in interphase and might be worth considering in a pharmacological perspective.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aurora Kinase B
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Aurora Kinases
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Cell Line, Tumor
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HeLa Cells
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Humans
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Interphase
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Microtubules / drug effects*
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Microtubules / physiology
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Organophosphates / chemistry
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Organophosphates / pharmacology*
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology*
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Protein Serine-Threonine Kinases / metabolism
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Quinazolines / chemistry
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Quinazolines / pharmacology*
Substances
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2-((3-((4-((5-(2-((3-fluorophenyl)amino)-2-oxoethyl)-1H-pyrazol-3-yl)amino)quinazolin-7-yl)oxy)propyl)(ethyl)amino)ethyl dihydrogen phosphate
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Organophosphates
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Protein Kinase Inhibitors
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Quinazolines
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AURKB protein, human
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Aurora Kinase B
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Aurora Kinases
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Protein Serine-Threonine Kinases