A screen for kinetochore-microtubule interaction inhibitors identifies novel antitubulin compounds.

ABSTRACT:

Background

Protein assemblies named kinetochores bind sister chromatids to the mitotic spindle and orchestrate sister chromatid segregation. Interference with kinetochore activity triggers a spindle checkpoint mediated arrest in mitosis, which frequently ends in cell death. We set out to identify small compounds that inhibit kinetochore-microtubule binding for use in kinetochore-spindle interaction studies and to develop them into novel anticancer drugs.

Methodology/principal findings

A fluorescence microscopy-based in vitro assay was developed to screen compound libraries for molecules that prevented the binding of a recombinant human Ndc80 kinetochore complex to taxol-stabilized microtubules. An active compound was identified that acted at the microtubule level. More speci

SUBMITTER: Screpanti E 

PROVIDER: S-EPMC2904697 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature