An ent-kaurene that inhibits mitotic chromosome movement and binds the kinetochore protein ran-binding protein 2.

Natalie T. Rundle, Jim Nelson, Mark R. Flory, Jomon Joseph, John Th'ng, Ruedi Aebersold, Mary Dasso, Raymond J. Andersen, Michel Roberge

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Using a chemical genetics screen, we have identified ent-15-oxokaurenoic acid (EKA) as a chemical that causes prolonged mitotic arrest at a stage resembling prometaphase. EKA inhibits the association of the mitotic motor protein centromeric protein E with kinetochores and inhibits chromosome movement. Unlike most antimitotic agents, EKA does not inhibit the polymerization or depolymerization of tubulin. To identify EKA-interacting proteins, we used a cell-permeable biotinylated form that retains biological activity to isolate binding proteins from living cells. Mass spectrometric analysis identified six EKA-binding proteins, including Ran-binding protein 2, a kinetochore protein whose depletion by small interfering RNA causes a similar mitotic arrest phenotype.

Original languageEnglish (US)
Pages (from-to)443-450
Number of pages8
JournalACS chemical biology
Volume1
Issue number7
DOIs
StatePublished - Aug 22 2006

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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    Rundle, N. T., Nelson, J., Flory, M. R., Joseph, J., Th'ng, J., Aebersold, R., Dasso, M., Andersen, R. J., & Roberge, M. (2006). An ent-kaurene that inhibits mitotic chromosome movement and binds the kinetochore protein ran-binding protein 2. ACS chemical biology, 1(7), 443-450. https://doi.org/10.1021/cb600196w