Study: Protein Blocks Cell Division

Washington, D.C. (AP) -- Researchers at Harvard Medical School have found the first of a new class of proteins that block cell division. The discovery eventually could lead to a new type of cancer drug. In a study to be published Friday in the journal Science, Harvard scientist Tim Mitchison and Stuart Schrieber describe discovery of a molecule that disrupts a key step in the process of cell division. The compound, called monastrol, blocks cell division in a different way from many of the current cancer drugs, the researchers said. Mitchison said in a statement that the discovery "represents a potential starting point for developing better chemotherapeutics" against cancer.

Spindle Specters... DNA is replicated during the S-phase of the cell cycle and condenses into discrete chromosomes during Mitosis (M-phase). Chromosomes are segregated equally into daughter cells by the microtubule-based structure called the spindle . Drugs that prevent assembly of tubulin into microtubules cause cell cycle arrest because the spindle does not form. Monastrol, on the other hand, causes cell cycle arrest by disrupting another target, a kinesin-related motor protein that is necessary for formation of a bipolar spindle.



Thomas U. Mayer [Department of Cell Biology and Institute of Chemistry and Cell Biology, Harvard Medical School; Boston, MA 02115; USA; E-mail: Thomas_Mayer@hms.harvard.edu ], Tarun M. Kapoor, Stephen J. Haggarty, Randall W. King, Stuart L. Schreiber, Timothy J. Mitchison , "Small Molecule Inhibitor of Mitotic Spindle Bipolarity Identified in a Phenotype-Based Screen" Science, Vol. 286, No. 5441, pp. 971 - 974 (October 29, 1999).

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 post-translational 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, 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.