Pharmacological inhibition of aurora-A but not aurora-B impairs interphase microtubule dynamics.
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.
Lorenzo
Corinne
C
Université de Toulouse, LBCMCP, Toulouse, France.
Liao
Qiaoyin
Q
Hardwicke
Mary Ann
MA
Ducommun
Bernard
B
D064107:Aurora Kinase B; D064127:Aurora Kinases; D045744:Cell Line, Tumor; D006367:HeLa Cells; D006801:Humans; D007399:Interphase; D008870:Microtubules / Q000187:drug effects* / Q000502:physiology; D010755:Organophosphates / Q000737:chemistry / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology*
C520647:2-((3-((4-((5-(2-((3-fluorophenyl)amino)-2-oxoethyl)-1H-pyrazol-3-yl)amino)quinazolin-7-yl)oxy)propyl)(ethyl)amino)ethyl dihydrogen phosphate; D010755:Organophosphates; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases