Journal ArticleDOI
Microtubule targeting agents: from biophysics to proteomics
David Calligaris,Pascal Verdier-Pinard,François Devred,Claude Villard,Diane Braguer,Daniel Lafitte +5 more
Reads0
Chats0
TLDR
This review explores various aspects of the interaction between microtubule targeting agents and tubulin, including binding site, affinity, and drug resistance, and how the three-dimensional structures of drug–tubulin complexes obtained on stabilized tubulin are seeded by precise biological and biophysical data.Abstract:
This review explores various aspects of the interaction between microtubule targeting agents and tubulin, including binding site, affinity, and drug resistance Starting with the basics of tubulin polymerization and microtubule targeting agent binding, we then highlight how the three-dimensional structures of drug-tubulin complexes obtained on stabilized tubulin are seeded by precise biological and biophysical data New avenues opened by thermodynamics analysis, high throughput screening, and proteomics for the molecular pharmacology of these drugs are presented The amount of data generated by biophysical, proteomic and cellular techniques shed more light onto the microtubule-tubulin equilibrium and tubulin-drug interaction Combining these approaches provides new insight into the mechanism of action of known microtubule interacting agents and rapid in-depth characterization of next generation molecules targeting the interaction between microtubules and associated modulators of their dynamics This will facilitate the design of improved and/or alternative chemotherapies targeting the microtubule cytoskeletonread more
Citations
More filters
Journal ArticleDOI
Microtubule destabilising agents: far more than just antimitotic anticancer drugs.
Darcy J. P. Bates,Alan Eastman +1 more
TL;DR: The numerous cellular consequences of disrupting microtubules dynamics are highlighted, expanding the textbook knowledge of microtubule destabilising agents and providing novel opportunities for their use in cancer therapy.
Journal ArticleDOI
End-binding proteins sensitize microtubules to the action of microtubule-targeting agents
Renu Mohan,Eugene A. Katrukha,Harinath Doodhi,Ihor Smal,Erik Meijering,Lukas C. Kapitein,Michel O. Steinmetz,Anna Akhmanova +7 more
TL;DR: This analysis indicated that MTAs affect microtubule aging in multiple ways: destabilizing MTAs, such as colchicine and vinblastine, accelerate aging in an EB-dependent manner, whereas stabilizingMTAs,such as paclitaxel and peloruside A, induce not only catastrophes but also rescues and can reverse the aging process.
Journal ArticleDOI
Microtubule-targeted agents: when mitochondria become essential to chemotherapy.
TL;DR: The aim of the present contribution is to provide elements that could answer the question: how far are mitochondria essential to anticancer chemotherapy that targets the microtubule cytoskeleton?
Journal ArticleDOI
Downregulation of KIF23 suppresses glioma proliferation.
Satoshi Takahashi,Noemi Fusaki,Shigeki Ohta,Yoshihiro Iwahori,Yukihiko Iizuka,Kohei Inagawa,Yutaka Kawakami,Kazunari Yoshida,Masahiro Toda +8 more
TL;DR: Results indicate that downregulation of KIF23 decreases proliferation of glioma cells and that Kif23 may be a novel therapeutic target in malignant gliomas.
References
More filters
Journal ArticleDOI
Structure of the alpha beta tubulin dimer by electron crystallography.
TL;DR: An atomic model of the αβ tubulin dimer fitted to a 3.7-Å density map obtained by electron crystallography of zinc-induced tubulin sheets is presented.
Journal ArticleDOI
Expression of a multidrug-resistance gene in human tumors and tissues
TL;DR: The results suggest that measurement of mdr1 RNA may prove to be a valuable tool in the design of chemotherapy protocols and controlled clinical studies will be required.
Journal ArticleDOI
Refined structure of alpha beta-tubulin at 3.5 A resolution.
TL;DR: In this paper, a refined model of the alpha-beta-tubulin dimer was presented, which includes residues alpha: 2-34, alpha:61-439, beta:2-437, one molecule of GTP, one of GDP, and one of taxol, as well as one magnesium ion near the M-loop in the alpha subunit.
Journal ArticleDOI
Tracking the ends: a dynamic protein network controls the fate of microtubule tips
TL;DR: This work has shown that microtubule plus-end tracking proteins, a diverse group of evolutionarily conserved cellular factors that accumulate at the ends of growing microtubules, form dynamic networks through the interaction of a limited set of protein modules, repeat sequences and linear motifs that bind to each other with moderate affinities.