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

TitleAn ent-kaurene that inhibits mitotic chromosome movement and binds the kinetochore protein Ran-binding protein 2
Publication TypeJournal Article
Year of Publication2006
AuthorsRundle, NT, Nelson, J, Flory, MR, Joseph, J, Th’ng, J, Aebersold, R, Dasso, M, Andersen, RJ, Roberge, M
JournalAcs Chemical Biology
Volume1
Pagination443-450
ISBN Number1554-8929
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.

URL<Go to ISI>://000243894000018