Parallel chemical genetic and genome-wide RNAi screens identify cytokinesis inhibitors and targets

Cytokinesis involves temporally and spatially coordinated action of the cell cycle and cytoskeletal and membrane systems to achieve separation of daughter cells. To dissect cytokinesis mechanisms it would be useful to have a complete catalog of the proteins involved, and small molecule tools for spe...

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Bibliographic Details
Published in:PLoS biology 2004-12, Vol.2 (12), p.e379-e379
Main Authors: Eggert, Ulrike S, Kiger, Amy A, Richter, Constance, Perlman, Zachary E, Perrimon, Norbert, Mitchison, Timothy J, Field, Christine M
Format: Article
Language:English
Subjects:
Animals
Aurora Kinases
Caenorhabditis elegans
Cell Biology
Cell division
Cell Line
Cytokinesis
Drosophila
Formamides - pharmacology
Genetic Techniques
Genetics/Genomics/Gene Therapy
Genome
Genomes
Genomics - methods
Insects
Kinases
Microscopy, Fluorescence
Phenotype
Protein-Serine-Threonine Kinases - metabolism
Proteins
Pyrazoles - chemical synthesis
Pyrazoles - pharmacology
RNA Interference
Saccharomyces cerevisiae
Systems Biology
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Summary:Cytokinesis involves temporally and spatially coordinated action of the cell cycle and cytoskeletal and membrane systems to achieve separation of daughter cells. To dissect cytokinesis mechanisms it would be useful to have a complete catalog of the proteins involved, and small molecule tools for specifically inhibiting them with tight temporal control. Finding active small molecules by cell-based screening entails the difficult step of identifying their targets. We performed parallel chemical genetic and genome-wide RNA interference screens in Drosophila cells, identifying 50 small molecule inhibitors of cytokinesis and 214 genes important for cytokinesis, including a new protein in the Aurora B pathway (Borr). By comparing small molecule and RNAi phenotypes, we identified a small molecule that inhibits the Aurora B kinase pathway. Our protein list provides a starting point for systematic dissection of cytokinesis, a direction that will be greatly facilitated by also having diverse small molecule inhibitors, which we have identified. Dissection of the Aurora B pathway, where we found a new gene and a specific small molecule inhibitor, should benefit particularly. Our study shows that parallel RNA interference and small molecule screening is a generally useful approach to identifying active small molecules and their target pathways.
ISSN:1545-7885
1544-9173
1545-7885
DOI:10.1371/journal.pbio.0020379