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Small Molecule Inhibitor of Mitotic Spindle Bipolarity Identified in a Phenotype-Based Screen

Science  29 Oct 1999:
Vol. 286, Issue 5441, pp. 971-974
DOI: 10.1126/science.286.5441.971

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Abstract

Small molecules that perturb specific protein functions are valuable tools for dissecting complex processes in mammalian cells. A combination of two phenotype-based screens, one based on a specific posttranslational modification, the other visualizing microtubules and chromatin, was used to identify compounds that affect mitosis. One compound, here named monastrol, arrested mammalian cells in mitosis with monopolar spindles. In vitro, monastrol specifically inhibited the motility of the mitotic kinesin Eg5, a motor protein required for spindle bipolarity. All previously known small molecules that specifically affect the mitotic machinery target tubulin. Monastrol will therefore be a particularly useful tool for studying mitotic mechanisms.

  • * To whom correspondence should be addressed. E-mail: Thomas_Mayer{at}hms.harvard.edu

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