1. Identification of a Novel Protein Regulating Microtubule Stability through a Chemical Approach
- Author
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Wignall, Sarah M., Gray, Nathanael S., Chang, Young-Tae, Juarez, Lolita, Jacob, Richard, Al Burlingame, Schultz, Peter G., and Heald, Rebecca
- Subjects
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MICROTUBULES , *CYTOSKELETON , *MORPHOGENESIS - Abstract
To identify novel proteins regulating the microtubule cytoskeleton, we screened a library of purine derivatives using mitotic spindle assembly in Xenopus egg extracts as an assay. Out of a collection of 1561 compounds, we identified 15 that destabilized microtubules without targeting tubulin directly, resulting in small spindles. Affinity chromatography with one compound, named diminutol, revealed a potential target as NQO1, an NADP-dependent oxidoreductase. A role for NQO1 in influencing microtubule polymerization was confirmed through inhibition studies using known inhibitors and immunodepletion. Therefore, this chemical approach has identified a novel factor required for microtubule morphogenesis and cell division. [Copyright &y& Elsevier]
- Published
- 2004
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