ArticleProceedings of the National Academy of Sciences of the United States of America2016
2-(m-Azidobenzoyl)taxol binds differentially to distinct β-tubulin isotypes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- An evolution-conserved allosteric network in human tubulin governs paclitaxel efficacy.Nature chemical biology · 2026Article
- Review
- Imbalance between Actin Isoforms Contributes to Tumour Progression in Taxol-Resistant Triple-Negative Breast Cancer Cells.International journal of molecular sciences · 2024Article
- Taxol acts differently on different tubulin isotypes.Communications biology · 2023Article
- Discovery and development of botanical natural products and their analogues as therapeutics for ovarian cancer.Natural product reports · 2023Review
- βIII-tubulin suppression enhances the activity of Amuvatinib to inhibit cell proliferation in c-Met positive non-small cell lung cancer cells.Cancer medicine · 2023Article
- Small molecule photocatalysis enables drug target identification via energy transfer.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Utilization of Photoaffinity Labeling to Investigate Binding of Microtubule Stabilizing Agents to P-Glycoprotein and β-Tubulin.Journal of natural products · 2022Review
- The Effect of Tau and Taxol on Polymerization of MCF7 Microtubules In Vitro.International journal of molecular sciences · 2022Article
- The microtubule cytoskeleton: An old validated target for novel therapeutic drugs.Frontiers in pharmacology · 2022Review
- Taxol and β-tubulins from endophytic fungi isolated from the Himalayan Yew,Frontiers in microbiology · 2022Article
- PRPF6 promotes metastasis and paclitaxel resistance of ovarian cancer via SNHG16/CEBPB/GATA3 axis.Oncology research · 2021Article
- Mechanisms of Taxane ResistanceCancers · 2020Review
- Review
- Binding modes of cabazitaxel with the different human β-tubulin isotypes: DFT and MD studies.Journal of molecular modeling · 2020Article
- CPEB4-Promoted Paclitaxel Resistance in Ovarian CancerFrontiers in pharmacology · 2020Article
- Tubulin-VDAC Interaction: Molecular Basis for Mitochondrial Dysfunction in Chemotherapy-Induced Peripheral Neuropathy.Frontiers in physiology · 2019Article
- Taxol Analogues Exhibit Differential Effects on Photoaffinity Labeling of β-Tubulin and the Multidrug Resistance Associated P-Glycoprotein.Journal of natural products · 2018Article
- Article
- β-tubulin carboxy-terminal tails exhibit isotype-specific effects on microtubule dynamics in human gene-edited cells.Life science alliance · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
There are seven β-tubulin isotypes present in distinct quantities in mammalian cells of different origin. Altered expression of β-tubulin isotypes has been reported in cancer cell lines resistant to microtubule stabilizing agents (MSAs) and in human tumors resistant to Taxol. To study the relative binding affinities of MSAs, tubulin from different sources, with distinct β-tubulin isotype content, were specifically photolabeled with a tritium-labeled Taxol analog, 2-(m-azidobenzoyl)taxol, alone or in the presence of MSAs. The inhibitory effects elicited by these MSAs on photolabeling were distinct for β-tubulin from different sources. To determine the exact amount of drug that binds to different β-tubulin isotypes, bovine brain tubulin was photolabeled and the isotypes resolved by high-resolution isoelectrofocusing. All bands were analyzed by mass spectrometry following cyanogen bromide digestion, and the identity and relative quantity of each β-tubulin isotype determined. It was found that compared with other β-tubulin isotypes, βIII-tubulin bound the least amount of 2-(m-azidobenzoyl)taxol. Analysis of the sequences of β-tubulin near the Taxol binding site indicated that, in addition to the M-loop that is known to be involved in drug binding, the leucine cluster region of βIII-tubulin contains a unique residue, alanine, at 218, compared with other isotypes that contain threonine. Molecular dynamic simulations indicated that the frequency of Taxol-accommodating conformations decreased dramatically in the T218A variant, compared with other β-tubulins. Our results indicate that the difference in residue 218 in βIII-tubulin may be responsible for inhibition of drug binding to this isotype, which could influence downstream cellular events.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.