Drugs that target dynamic microtubules: a new molecular perspective.
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TLDR
The effects of microtubule‐binding chemotherapeutic agents are reviewed from a new perspective, considering how their mode of binding induces conformational changes and alters biological function relative to the molecular vectors of micro Tubule assembly or disassembly.Abstract:
Microtubules have long been considered an ideal target for anticancer drugs because of the essential role they play in mitosis, forming the dynamic spindle apparatus. As such, there is a wide variety of compounds currently in clinical use and in development that act as antimitotic agents by altering microtubule dynamics. Although these diverse molecules are known to affect microtubule dynamics upon binding to one of the three established drug domains (taxane, vinca alkaloid, or colchicine site), the exact mechanism by which each drug works is still an area of intense speculation and research. In this study, we review the effects of microtubule-binding chemotherapeutic agents from a new perspective, considering how their mode of binding induces conformational changes and alters biological function relative to the molecular vectors of microtubule assembly or disassembly. These “biological vectors” can thus be used as a spatiotemporal context to describe molecular mechanisms by which microtubule-targeting drugs work.read more
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References
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Journal ArticleDOI
Microtubules as a target for anticancer drugs.
Mary Ann Jordan,Leslie Wilson +1 more
TL;DR: Highly dynamic mitotic-spindle microtubules are among the most successful targets for anticancer therapy, and it is now known that at lower concentrations, microtubule-targeted drugs can suppress micro Tubule dynamics without changingmicrotubule mass; this action leads to mitotic block and apoptosis.
Journal ArticleDOI
Dynamic instability of microtubule growth
TL;DR: It is reported here that microtubules in vitro coexist in growing and shrinking populations which interconvert rather infrequently and this dynamic instability is a general property of micro Tubules and may be fundamental in explaining cellular microtubule organization.
Journal ArticleDOI
Microtubule polymerization dynamics
TL;DR: This review describes progress toward understanding the mechanism of dynamic instability of pure tubulin and discusses the function and regulation of microtubule dynamic instability in living cells.
Journal ArticleDOI
Kinesin and Dynein Superfamily Proteins and the Mechanism of Organelle Transport
TL;DR: This review focuses on the molecular mechanism of organelle transport in cells and describes kinesin and dynein superfamily proteins.
Journal ArticleDOI
Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain
Raimond B. G. Ravelli,Benoît Gigant,Patrick A. Curmi,Isabelle Jourdain,Sylvie Lachkar,André Sobel,Marcel Knossow +6 more
TL;DR: Changes in the subunits of tubulin as it switches from its straight conformation to a curved one correlate with the loss of lateral contacts and provide a rationale for the rapid microtubule depolymerization characteristic of dynamic instability.
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