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Differential Effects of Natural Product Microtubule Stabilizers on Microtubule Assembly: Single Agent and Combination Studies with Taxol, Epothilone B, and Discodermolide
Author(s) -
Gertsch Jürg,
Meier Sarah,
Müller Martin,
Altmann KarlHeinz
Publication year - 2009
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200800556
Subject(s) - tubulin , microtubule , isotype , epothilone , chemistry , biophysics , stereochemistry , biology , microbiology and biotechnology , antibody , immunology , monoclonal antibody
A systematic comparison has been performed of the morphology and stability of microtubules (MTs) induced by the potent microtubule‐stabilizing agents (MSAs) taxol, epothilone B (Epo B), and discodermolide (DDM) under GTP‐free conditions. DDM‐induced tubulin polymerization occurred significantly faster than that induced by taxol and Epo B. At the same time, tubulin polymers assembled from soluble tubulin by DDM were morphologically distinct (shorter and less ordered) from those induced by either taxol or Epo B, as demonstrated by electron microscopy. Exposure of MSA‐induced tubulin polymers to ultrasound revealed the DDM‐based polymers to be less stable to this type of physical stress than those formed with either Epo B or taxol. Interestingly, MT assembly in the presence of both DDM and taxol appeared to produce a distinct new type of MT polymer with a mixed morphology between those of DDM‐ and taxol‐induced structures. The observed differences in MT morphology and stability might be related, at least partly, to differences in intramicrotubular tubulin isotype distribution, as DDM showed a different pattern of β‐tubulin isotype usage in the assembly process.