期刊
CHEMISTRY & BIOLOGY
卷 11, 期 1, 页码 135-146出版社
CELL PRESS
DOI: 10.1016/j.chembiol.2003.12.019
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资金
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM057839] Funding Source: NIH RePORTER
- NIGMS NIH HHS [GM57839] Funding Source: Medline
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.
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