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taxol crystals can masquerade as stabilized microtubules紫杉醇晶体可以伪装成稳定微管
Taxol Crystals Can Masquerade as Stabilized
Microtubules
Margit Foss1., Buck W. L. Wilcox2., G. Bradley Alsop2¤, Dahong Zhang1,3*
1 Department of Zoology, Oregon State University, Corvallis, Oregon, United States of America, 2 Molecular and Cellular Biology Program, Oregon
State University, Corvallis, Oregon, United States of America, 3 Center for Genome Research and Biocomputing, Oregon State University, Corvallis,
Oregon, United States of America
Taxol is a potent anti-mitotic drug used in chemotherapy, angioplastic stents, and cell biology research. By binding and
stabilizing microtubules, Taxol inhibits their dynamics, crucial for cell division, motility, and survival. The drug has also been
reported to induce formation of asters and bundles composed of stabilized microtubules. Surprisingly, at commonly used
concentrations, Taxol forms crystals that rapidly bind fluorescent tubulin subunits, generating structures with an uncanny
resemblance to microtubule asters and bundles. Kinetic and topological considerations suggest that tubulin subunits, rather
than microtubules, bind the crystals. This sequestration of tubulin from the subunit pool would be expected to shift the
equilibrium of free to polymerized tubulin to disfavor assembly. Our results imply that some previously reported Taxol-
induced asters or bundles could include or be composed of tubulin-decorated Taxol crystals. Thus, reevaluation of certain
morphological, chemical, and physical properties of Taxol-treated microtubules may be necessary. Moreover, our findings
suggest a novel mechanism for chemotherapy-induced cytotoxicity in non-dividing cells, with far-reaching medical
implications.
Citation: Foss M, Wilcox BWL, Alsop GB, Zhang D (2008) Taxol Crystals Can Masquerade as Stabilized Microtubules. PL
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