title: Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen.
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.
authors.affiliation: Department of Cell Biology, and Institute of Chemistry and Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Thomas_Mayer@hms.harvard.edu
authors.forename: T U
authors.initials: TU
authors.lastname: Mayer
authors.forename: T M
authors.initials: TM
authors.lastname: Kapoor
authors.forename: S J
authors.initials: SJ
authors.lastname: Haggarty
authors.forename: R W
authors.initials: RW
authors.lastname: King
authors.forename: S L
authors.initials: SL
authors.lastname: Schreiber
authors.forename: T J
authors.initials: TJ
authors.lastname: Mitchison
mesh_terms: D000199:Actins / Q000187:drug effects; D000818:Animals; D002417:Cattle; D002460:Cell Line; D003599:Cytoskeleton / Q000187:drug effects; D006056:Golgi Apparatus / Q000187:drug effects; D016547:Kinesins / Q000187:drug effects*; D008870:Microtubules / Q000187:drug effects; D008938:Mitosis / Q000187:drug effects*; D020409:Molecular Motor Proteins / Q000187:drug effects; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011743:Pyrimidines / Q000494:pharmacology*; D016601:RNA-Binding Proteins / Q000378:metabolism; D008941:Spindle Apparatus / Q000187:drug effects*; D013871:Thiones / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014981:Xenopus; D029867:Xenopus Proteins; D000097796:Nucleolin
chemical_list: D000199:Actins; D016547:Kinesins; D020409:Molecular Motor Proteins; D010750:Phosphoproteins; D011743:Pyrimidines; D016601:RNA-Binding Proteins; D013871:Thiones; D029867:Xenopus Proteins; D000097796:Nucleolin; C088335:KIF11 protein, Xenopus; C400223:monastrol