Taxol assembles tubulin in the absence of exogenous guanosine 5'-triphosphate or microtubule-associated proteins

Biochemistry. 1981 May 26;20(11):3247-52. doi: 10.1021/bi00514a041.

Abstract

Taxol increases the rate and extent of microtubule assembly in vitro and stabilizes microtubules in vitro and in cells [Schiff, P. B., Fant, J., & Horwitz, S. B. (1979) Nature (London) 277, 665-667; Schiff, P. B., & Horwitz, S. B. (1980) Proc. Natl. Acad. Sci. U.S.A. 77, 1561-1565]. We report herein that taxol has the ability to promote microtubule assembly in the absence of microtubule-associated proteins, rings, and added guanosine 5'-triphosphate (GTP or organic buffer. The drug enhances additional microtubule assembly when added to microtubules at apparent steady state. This additional assembly can be attributed to both elongation of existing microtubules and spontaneous nucleation of new microtubules. Taxol-treated microtubules have depressed dissociation reactions as determined by dilution experiments. The drug does not inhibit the binding of GTP or the hydrolysis of GTP or guanosine 5'-diphosphate (GDP) in our microtubule protein preparations. Taxol does not competitively inhibit the binding of colchicine to tubulin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Brain / metabolism
  • Cattle
  • Colchicine / metabolism
  • GTP Phosphohydrolases / metabolism
  • Guanosine Triphosphate / metabolism*
  • Kinetics
  • Microscopy, Electron
  • Microtubule-Associated Proteins
  • Microtubules / ultrastructure
  • Nerve Tissue Proteins / physiology*
  • Paclitaxel
  • Protein Binding
  • Proteins / physiology*
  • Terpenes / pharmacology*
  • Tubulin / metabolism*

Substances

  • Antineoplastic Agents, Phytogenic
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Proteins
  • Terpenes
  • Tubulin
  • Guanosine Triphosphate
  • GTP Phosphohydrolases
  • Paclitaxel
  • Colchicine