ArticleThe Journal of cell biology1986
Taxol-dependent mutants of Chinese hamster ovary cells with alterations in alpha- and beta-tubulin.
Article in The Journal of cell biology, 1986. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 122 citations in OpenAlex.
- Article
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- Zampanolide, a Microtubule-Stabilizing Agent, Is Active in Resistant Cancer Cells and Inhibits Cell Migration.International journal of molecular sciences · 2017Article
- Paclitaxel Through the Ages of Anticancer Therapy: Exploring Its Role in Chemoresistance and Radiation Therapy.Cancers · 2015Review
- Drug discovery targeting cell division proteins, microtubules and FtsZ.Bioorganic & medicinal chemistry · 2014Review
- Protein kinase A type II-α regulatory subunit regulates the response of prostate cancer cells to taxane treatment.Cell cycle (Georgetown, Tex.) · 2014Article
- Increased α-tubulin1b expression indicates poor prognosis and resistance to chemotherapy in hepatocellular carcinoma.Digestive diseases and sciences · 2013Article
- Response to microtubule-interacting agents in primary epithelial ovarian cancer cells.Cancer cell international · 2013Article
- The role of microtubules and their dynamics in cell migration.The Journal of biological chemistry · 2012Article
- Random mutagenesis of β-tubulin defines a set of dispersed mutations that confer paclitaxel resistance.Pharmaceutical research · 2012Article
- New insights into mechanisms of resistance to microtubule inhibitors.Biochimica et biophysica acta · 2011Review
- Mitotic centromere-associated kinesin (MCAK) mediates paclitaxel resistance.The Journal of biological chemistry · 2011Article
- Mutations in the β-tubulin binding site for peloruside A confer resistance by targeting a cleft significant in side chain binding.Cell cycle (Georgetown, Tex.) · 2011Article
- Modulating microtubule stability enhances the cytotoxic response of cancer cells to Paclitaxel.Cancer research · 2011Article
- Design, synthesis, biological evaluation, and structure-activity relationships of substituted phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates as new tubulin inhibitors mimicking combretastatin A-4.Journal of medicinal chemistry · 2011Article
- Overexpression of mitotic centromere-associated Kinesin stimulates microtubule detachment and confers resistance to paclitaxel.Molecular cancer therapeutics · 2011Article
- Paclitaxel-dependent cell lines reveal a novel drug activity.Molecular cancer therapeutics · 2010Article
- Inhibition of cell migration and cell division correlates with distinct effects of microtubule inhibiting drugs.The Journal of biological chemistry · 2010Article
- Metronomic chemotherapy: new rationale for new directions.Nature reviews. Clinical oncology · 2010Review
- Human mutations that confer paclitaxel resistance.Molecular cancer therapeutics · 2010Article
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2 authors.
Funding
Abstract
Chinese hamster ovary cell mutants resistant to the microtubule stabilizing drug taxol were isolated in a single step. Of these 139 drug-resistant mutants, 59 exhibit an absolute requirement for taxol for normal growth and division, 13 have a partial requirement, and 69 grow normally without the drug. Two-dimensional gel analysis of whole cell proteins reveal "extra" spots representing altered tubulins in 13 of the mutants. Six of these have an altered alpha-tubulin and seven have an altered beta-tubulin. Cells with an absolute dependence on taxol become large and multinucleated when deprived of the drug. In contrast, partially dependent cells exhibit some multinucleation, but most cells appear normal. In one mutant that has an absolute dependence on taxol, the cells appear to die more quickly and their nuclei do not increase in size or number. As previously found for another taxol-dependent mutant (Cabral, F., 1983, J. Cell. Biol., 97:22-29), the taxol dependence of the mutants described in this paper behaves recessively in somatic cell hybrids, and the cells are more susceptible to being killed by colcemid than are the wild-type parental cells. When compared with wild-type cells, taxol-dependent mutants have normal arrays of cytoplasmic microtubules but form much smaller mitotic spindles in the presence of taxol. When deprived of the drug, however, these mutants cannot complete assembly of the mitotic spindle apparatus, as judged by tubulin immunofluorescence. Thus, the defects leading to taxol dependence in these mutants with defined alterations in alpha- and beta-tubulin appear to result from the cell's inability to form a functional mitotic spindle. Reversion analysis indicates that the properties of at least one alpha-tubulin mutant are conferred by the altered tubulin seen on two-dimensional gels.
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