Identification of a Novel Protein Regulating Microtubule Stability through a Chemical Approach

Sarah M. Wignall, Nathanael S. Gray, Young Tae Chang, Lolita Juarez, Richard Jacob, A. Burlingame, Peter G. Schultz, Rebecca Heald*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)135-146
Number of pages12
JournalChemistry and Biology
Issue number1
StatePublished - Jan 2004

ASJC Scopus subject areas

  • Drug Discovery
  • Molecular Medicine
  • Molecular Biology
  • Biochemistry
  • Clinical Biochemistry
  • Pharmacology


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