ArticleProceedings of the National Academy of Sciences of the United States of America2006
Insights into the mechanism of microtubule stabilization by Taxol.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 174 papers.
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Who cites it
174 citing papers in PubMed, 327 citations in OpenAlex.
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- In vitro effects of Taurine on Taxol-induced mitochondrial dysfunction.Proceedings of SPIE--the International Society for Optical Engineering · 2026Article
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- The biosynthesis and diversity of taxanes: From pathway elucidation to engineering and synthetic biology.Plant communications · 2025Review
- NEK Family Kinases: Structure, Function, and Role in Disease.Biomolecules · 2025Review
- Stem cell mechanoadaptation. I. Effect of microtubule stabilization and volume changing stresses on cytoskeletal remodeling.APL bioengineering · 2025Article
- Development and validation of a functional ex vivo paclitaxel and eribulin sensitivity assay for breast cancer, the REMIT assay.NPJ breast cancer · 2025Article
- Biliary atresia: insights into mechanisms using a toxic model of the disease including Wnt and Hippo signaling pathways and microtubules.Pediatric research · 2025Article
- The tubulin polymerization inhibitor gambogenic acid induces myelodysplastic syndrome cell apoptosis through upregulation of Fas expression mediated by the NF-κB signaling pathway.Cancer biology & therapy · 2024Article
- Microtubule acetylation and PERK activation facilitate eribulin-induced mitochondrial calcium accumulation and cell death.Cellular and molecular life sciences : CMLS · 2024Article
- KLP-7/Kinesin-13 orchestrates axon-dendrite checkpoints for polarized trafficking in neurons.Molecular biology of the cell · 2024Article
- Regulation of microtubule dynamics and function in living cellsChemical science · 2024Article
- Misregulation of bromotyrosine compromises fertility in maleProceedings of the National Academy of Sciences of the United States of America · 2024Article
- New Insights into Chemoresistance Mediated by Mdm2 Inhibitors: The Benefits of Targeted Therapy over Common Cytostatics.Biomedicines · 2024Article
114 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The antitumor drug Taxol stabilizes microtubules and reduces their dynamicity, promoting mitotic arrest and cell death. Upon assembly of the alpha/beta-tubulin heterodimer, GTP bound to beta-tubulin is hydrolyzed to GDP reaching a steady-state equilibrium between free tubulin dimers and microtubules. The binding of Taxol to beta-tubulin in the polymer results in cold-stable microtubules at the expense of tubulin dimers, even in the absence of exogenous GTP. However, there is little biochemical insight into the mechanism(s) by which Taxol stabilizes microtubules. Here, we analyze the structural changes occurring in both beta- and alpha-tubulin upon microtubule stabilization by Taxol. Hydrogen/deuterium exchange (HDX) coupled to liquid chromatography-electrospray ionization MS demonstrated a marked reduction in deuterium incorporation in both beta-and alpha-tubulin when Taxol was present. Decreased local HDX in peptic peptides was mapped on the tubulin structure and revealed both expected and new dimer-dimer interactions. The increased rigidity in Taxol microtubules was distinct from and complementary to that due to GTP-induced polymerization. The Taxol-induced changes in tubulin conformation act against microtubule depolymerization in a precise directional way. These results demonstrate that HDX coupled to liquid chromatography-electrospray ionization MS can be effectively used to study conformational effects induced by small ligands on microtubules. The present study also opens avenues for locating drug and protein binding sites and for deciphering the mechanisms by which their interactions alter the conformation of microtubules and tubulin dimers.
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