Manso-Martínez R
Mol Cell Biochem. 1982 May 28;45(1):3-11. doi: 10.1007/BF01283158.
Depolymerization kinetics of microtubules assembled to steady-state by podophyllotoxin treatment show a dose-dependent effect of this mitotic poison on the net rate of microtubule disassembly. Pulse-chase experiments with microtubules at steady-state indicate that the depolymerization effect induced by superstoichiometric concentrations of podophyllotoxin relative to tubulin is polar and time-dependent, i.e. the rate of tubulin loss decreases along with the time of treatment in the presence of the drug. Under these conditions the rate of microtubule disassembly is much faster than one could expect from a unique effect of drug-tubulin complex on the microtubule assembly end. Podophyllotoxin-tubulin complex is not able to induce active depolymerization of microtubules, while free podophyllotoxin is. These results are consistent with the hypothesis that this drug acts on the microtubule assembly-disassembly process by two different mechanisms: 1) as a free drug, it actively promotes polar depolymerization of microtubules, and 2) as a drug-tubulin complex, it retards the addition of subunits into the microtubule ends.
经鬼臼毒素处理组装至稳态的微管解聚动力学表明，这种有丝分裂毒物对微管解聚净速率具有剂量依赖性效应。对处于稳态的微管进行脉冲追踪实验表明，相对于微管蛋白超化学计量浓度的鬼臼毒素所诱导的解聚效应是极性的且与时间相关，即在药物存在的情况下，微管蛋白损失速率随处理时间而降低。在这些条件下，微管解聚速率比仅由药物 - 微管蛋白复合物对微管组装末端产生的独特效应所预期的要快得多。鬼臼毒素 - 微管蛋白复合物无法诱导微管的主动解聚，而游离的鬼臼毒素则可以。这些结果与以下假设一致：这种药物通过两种不同机制作用于微管组装 - 解聚过程：1）作为游离药物，它积极促进微管的极化解聚；2）作为药物 - 微管蛋白复合物，它阻碍亚基添加到微管末端。
