Aurora-A overexpression leads to override of the microtubule-kinetochore attachment checkpoint.
The amplification of AURORA-A is frequently observed in specific epithelial cell malignancies. The overexpression of aurora-A, a Ser-Thr kinase known to localize to centrosomes during mitosis, appears to imbue cancerous cells with resistance to spindle-checkpoint-targeting drugs such as paclitaxel (Taxol). Indeed, a recent publication by Anand et al. indicates that overexpression of AURORA-A may interfere with spindle-microtubule attachment and disrupt the regulation of the spindle checkpoint by allowing cells with abnormal chromosomal separation to enter anaphase. Thus, the design of new drugs that specifically target aurora-A rather than other checkpoint proteins might alleviate the resistance to Taxol-like clinical therapeutics observed in some tumors.
Groupe Cycle Cellulaire, UMR6061 CNRS-Université de Rennes 1, Faculté de Médecine, 2 Avenue du Pr Léon Bernard CS 34317, 35043 Rennes cedex, France. stephanie.dutertre@univ-rennes1.fr
Stéphanie
S
Dutertre
Claude
C
Prigent
D000705:Anaphase; D000818:Animals; D017209:Apoptosis; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017173:Caenorhabditis elegans; D002135:Calcium-Binding Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D002460:Cell Line; D018385:Centrosome / Q000648:ultrastructure; D004331:Drosophila melanogaster; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000648:ultrastructure*; D064246:Mad2 Proteins; D008677:Metaphase; D051379:Mice; D008870:Microtubules / Q000648:ultrastructure*; D008954:Models, Biological; D011494:Protein Kinases / Q000096:biosynthesis* / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae; D029867:Xenopus Proteins
D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D012097:Repressor Proteins; D029867:Xenopus Proteins; D011494:Protein Kinases; C112134:AURKA protein, Xenopus; C576918:Aurka protein, mouse; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases