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First published online August 24, 2006

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Cancer targets - Aurora B or alias

Aurora kinases regulate various aspects of mitosis and are therefore targets for potential new anti-cancer drugs. The Aurora A/B inhibitor ZM447439, for example, interferes with chromosome alignment, the spindle checkpoint and cytokinesis, making cells exit mitosis without dividing and die. Stephen Taylor and co-workers have combined chemical genetics and molecular genetics to establish whether this is due to inhibition of Aurora A or Aurora B - and thus gain further insights into the functions of these two kinases (see p. 3664). Closely analysing cell lines that stably express dominant negative forms of different Aurora kinases, they find that inhibition of Aurora B most closely mimics treatment of cells with ZM447439. Furthermore they find that a related compound, ZM2, that is much more specific for Aurora B has almost identical effects. By contrast, ZM3, which more potently inhibits Aurora A, produces a rather different phenotype - formation of monopolar spindles. The new work thus not only reveals that Aurora B is the critical target of ZM447439 but also establishes a role for Aurora A in generation of bipolar mitotic spindles.

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Related articles in JCS:

Validating Aurora B as an anti-cancer drug target

Fiona Girdler, Karen E. Gascoigne, Patrick A. Eyers, Sonya Hartmuth, Claire Crafter, Kevin M. Foote, Nicholas J. Keen, and Stephen S. Taylor
JCS 2006 119: 3664-3675. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?