Stathmin/Op18 is a novel mediator of vinblastine activity

Francois Devred, Philipp O. Tsvetkov, Pascale Barbier, Diane Allegro, Susan Band Horwitz, Alexander A. Makarov, Vincent Peyrot

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Microtubule (MT) dynamic instability is tightly regulated by stabilizing and destabilizing proteins, the latter being exemplified by stathmin/Op18, a protein known to destabilize MTs. Studies in cells have indicated that the level of stathmin expression modifies the cytotoxicity of antimicrotubule drugs, such as vinblastine (VLB). Using isothermal titration calorimetry and analytical ultracentrifugation, we show that VLB increases the affinity of stathmin for tubulin 50-fold (and vice versa). These results are the first biochemical evidence of the direct relationship between stathmin and an antimitotic drug, and reveal a new mechanism of action for VLB. Structured summary: MINT-6603918:tubulin beta (uniprotkb:Q9H4B7), tubulin alpha (uniprotkb:Q71U36) and stathmin (uniprotkb:Q71U36) physically interact (MI:0218) by cosedimentation (MI:0027)MINT-6603930:tubulin alpha (uniprotkb:Q71U36) physically interacts (MI:0218) with tubulin beta (uniprotkb:Q9H4B7) and stathmin (uniprotkb:P16949) by isothermal titration calorimetry (MI:0065).

Original languageEnglish (US)
Pages (from-to)2484-2488
Number of pages5
JournalFEBS Letters
Volume582
Issue number17
DOIs
StatePublished - Jul 23 2008

Keywords

  • Analytical ultracentrifugation
  • Isothermal titration calorimetry
  • Microtubule
  • Stathmin
  • Tubulin
  • Vinblastine

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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    Devred, F., Tsvetkov, P. O., Barbier, P., Allegro, D., Horwitz, S. B., Makarov, A. A., & Peyrot, V. (2008). Stathmin/Op18 is a novel mediator of vinblastine activity. FEBS Letters, 582(17), 2484-2488. https://doi.org/10.1016/j.febslet.2008.06.035