Taxol-induced polymerization of purified tubulin. Mechanism of action.
Incubation of tubulin with taxol resulted in the assembly of tubulin in the absence of microtubule associated proteins. Optimum assembly occurred at approximately equal concentrations of tubulin and taxol. Both podophyllotoxin and colchicine inhibited the taxol-induced tubulin polymerization. Microtubules formed with taxol were also resistant to podophyllotoxin-induced depolymerization. The rate of tubulin subunit exchange into taxol-induced microtubules at steady state was 5-fold lower than into microtubule-associated protein (MAP2)-stimulated microtubules. There was a marked difference in the kinetics of tubulin polymerized in the presence of both taxol and MAP2 as compared to that obtained with either of them alone. In binding experiments, no competition was observed between taxol and MAP2 or the anti-tubulin drugs, e.g. colchicine, podophyllotoxin, and vinblastine.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002417:Cattle; D007700:Kinetics; D046911:Macromolecular Substances; D008870:Microtubules / Q000378:metabolism; D017239:Paclitaxel; D011034:Podophyllotoxin / Q000494:pharmacology; D011485:Protein Binding; D014404:Tubulin / Q000378:metabolism*
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D046911:Macromolecular Substances; D014404:Tubulin; D011034:Podophyllotoxin; D017239:Paclitaxel