Stathmin/Op18 is a novel mediator of vinblastine activity.
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.
Devred
Francois
F
INSERM UMR 911, Centre de Recherche en Oncologie biologique et en Oncopharmacologie, Aix-Marseille Université, Faculté de Pharmacie, 13385 Marseille Cedex 5, France. francois.devred@pharmacie.univ-mrs.fr
Tsvetkov
Philipp O
PO
Barbier
Pascale
P
Allegro
Diane
D
Horwitz
Susan Band
SB
Makarov
Alexander A
AA
Peyrot
Vincent
V
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism* / Q000494:pharmacology*; D002478:Cells, Cultured; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D012756:Sheep; D050777:Stathmin / Q000378:metabolism*; D013816:Thermodynamics; D014404:Tubulin / Q000187:drug effects / Q000378:metabolism; D050257:Tubulin Modulators / Q000378:metabolism* / Q000494:pharmacology*; D014747:Vinblastine / Q000378:metabolism* / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D050777:Stathmin; D014404:Tubulin; D050257:Tubulin Modulators; D014747:Vinblastine