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Molecular Interventions 3:127-130 (2003)
© 2003 American Society of Pharmacology and Experimental Therapeutics

Viewpoint

Aurora-A Overexpression Leads to Override of the Microtubule-Kinetochore Attachment Checkpoint

Stéphanie Dutertre and Claude Prigent

Groupe Cycle Cellulaire, UMR6061 CNRS-Université de Rennes 1, Faculté de Médecine, 2 Avenue du Pr Léon Bernard CS 34317, 35043 Rennes cedex, France.

SUMMARY

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 interefere 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.




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Copyright © 2003 by the American Society for Pharmacology and Experimental Therapeutics.