Format

Send to

Choose Destination
Trends Cell Biol. 2018 Oct;28(10):776-792. doi: 10.1016/j.tcb.2018.05.001. Epub 2018 Jun 2.

Microtubule-Targeting Agents: Strategies To Hijack the Cytoskeleton.

Author information

1
Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, 5232 Villigen, Switzerland; University of Basel, Biozentrum, 4056 Basel, Switzerland. Electronic address: michel.steinmetz@psi.ch.
2
Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, 5232 Villigen, Switzerland. Electronic address: andrea.prota@psi.ch.

Abstract

Microtubule-targeting agents (MTAs) such as paclitaxel and the vinca alkaloids are among the most important medical weapons available to combat cancer. MTAs interfere with intracellular transport, inhibit eukaryotic cell proliferation, and promote cell death by suppressing microtubule dynamics. Recent advances in the structural analysis of MTAs have enabled the extensive characterization of their interactions with microtubules and their building block tubulin. We review here our current knowledge on the molecular mechanisms used by MTAs to hijack the microtubule cytoskeleton, and discuss dual inhibitors that target both kinases and microtubules. We further formulate some outstanding questions related to MTA structural biology and present possible routes for future investigations of this fascinating class of antimitotic agents.

KEYWORDS:

microtubule-targeting agents; molecular mechanisms of action; tubulin-ligand binding modes

PMID:
29871823
DOI:
10.1016/j.tcb.2018.05.001

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center