Stathmin/Op18 is a novel mediator of vinblastine activity

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

Abbreviations: ITC, isothermal titration calorimetry, VLB, vinblastine, T2S, complex of stathmin with two tubulin dimers, MT, microtubule, AUC, analytical ultracentrifugation

Keywords: Tubulin, Microtubule, Vinblastine, Stathmin, Isothermal titration calorimetry, Analytical ultracentrifugation