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 journalArticle

55 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)135-146
Number of pages12
JournalChemistry and Biology
Volume11
Issue number1
DOIs
StatePublished - Jan 2004

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Identification of a Novel Protein Regulating Microtubule Stability through a Chemical Approach'. Together they form a unique fingerprint.

  • Cite this

    Wignall, S. M., Gray, N. S., Chang, Y. T., Juarez, L., Jacob, R., Burlingame, A., Schultz, P. G., & Heald, R. (2004). Identification of a Novel Protein Regulating Microtubule Stability through a Chemical Approach. Chemistry and Biology, 11(1), 135-146. https://doi.org/10.1016/j.chembiol.2003.12.019