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

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

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 - Jan 1 2006
Externally publishedYes

Fingerprint

Kaurane Diterpenes
Kinetochores
Chromosomes
Protein Binding
Acids
Carrier Proteins
Proteins
Prometaphase
Antimitotic Agents
Depolymerization
Tubulin
Bioactivity
Polymerization
Small Interfering RNA
Cells
ran-binding protein 2
5-oxokaurenoic acid
Association reactions
Phenotype

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

An ent-kaurene that inhibits mitotic chromosome movement and binds the kinetochore protein ran-binding protein 2. / Rundle, Natalie T.; Nelson, Jim; Flory, Mark; Joseph, Jomon; Th'ng, John; Aebersold, Ruedi; Dasso, Mary; Andersen, Raymond J.; Roberge, Michel.

In: ACS chemical biology, Vol. 1, No. 7, 01.01.2006, p. 443-450.

Research output: Contribution to journalArticle

Rundle, NT, Nelson, J, Flory, M, Joseph, J, Th'ng, J, Aebersold, R, Dasso, M, Andersen, RJ & Roberge, M 2006, 'An ent-kaurene that inhibits mitotic chromosome movement and binds the kinetochore protein ran-binding protein 2.', ACS chemical biology, vol. 1, no. 7, pp. 443-450. https://doi.org/10.1021/cb600196w
Rundle, Natalie T. ; Nelson, Jim ; Flory, Mark ; Joseph, Jomon ; Th'ng, John ; Aebersold, Ruedi ; Dasso, Mary ; Andersen, Raymond J. ; Roberge, Michel. / An ent-kaurene that inhibits mitotic chromosome movement and binds the kinetochore protein ran-binding protein 2. In: ACS chemical biology. 2006 ; Vol. 1, No. 7. pp. 443-450.
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