| http://purl.uniprot.org/citations/21653684 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21653684 | http://www.w3.org/2000/01/rdf-schema#comment | "Peloruside A and laulimalide are potent microtubule-stabilizing natural products with a mechanism of action similar to that of paclitaxel. However, the binding site of peloruside A and laulimalide on tubulin remains poorly understood. Drug resistance in anticancer treatment is a serious problem. We developed peloruside A- and laulimalide-resistant cell lines by selecting 1A9 human ovarian carcinoma cells that were able to grow in the presence of one of these agents. The 1A9-laulimalide resistant cells (L4) were 39-fold resistant to the selecting agent and 39-fold cross-resistant to peloruside A, whereas the 1A9-peloruside A resistant cells (R1) were 6-fold resistant to the selecting agent while they remained sensitive to laulimalide. Neither cell line showed resistance to paclitaxel or other drugs that bind to the taxoid site on β-tubulin nor was there resistance to microtubule-destabilizing drugs. The resistant cells exhibited impaired peloruside A/laulimalide-induced tubulin polymerization and impaired mitotic arrest. Tubulin mutations were found in the βI-tubulin isotype, R306H or R306C for L4 and A296T for R1 cells. This is the first cell-based evidence to support a β-tubulin-binding site for peloruside A and laulimalide. To determine whether the different resistance phenotypes of the cells were attributable to any other tubulin alterations, the β-tubulin isotype composition of the cells was examined. Increased expression of βII- and βIII-tubulin was observed in L4 cells only. These results provide insight into how alterations in tubulin lead to unique resistance profiles for two drugs, peloruside A and laulimalide, that have a similar mode of action."xsd:string |
| http://purl.uniprot.org/citations/21653684 | http://purl.org/dc/terms/identifier | "doi:10.1158/1535-7163.mct-10-1057"xsd:string |
| http://purl.uniprot.org/citations/21653684 | http://purl.uniprot.org/core/author | "Chan A."xsd:string |
| http://purl.uniprot.org/citations/21653684 | http://purl.uniprot.org/core/author | "Miller J.H."xsd:string |
| http://purl.uniprot.org/citations/21653684 | http://purl.uniprot.org/core/author | "Crawford J."xsd:string |
| http://purl.uniprot.org/citations/21653684 | http://purl.uniprot.org/core/author | "Wilmes A."xsd:string |
| http://purl.uniprot.org/citations/21653684 | http://purl.uniprot.org/core/author | "Northcote P.T."xsd:string |
| http://purl.uniprot.org/citations/21653684 | http://purl.uniprot.org/core/author | "Rawson P."xsd:string |
| http://purl.uniprot.org/citations/21653684 | http://purl.uniprot.org/core/author | "Hamel E."xsd:string |
| http://purl.uniprot.org/citations/21653684 | http://purl.uniprot.org/core/author | "Giannakakou P."xsd:string |
| http://purl.uniprot.org/citations/21653684 | http://purl.uniprot.org/core/author | "O'Brate A."xsd:string |
| http://purl.uniprot.org/citations/21653684 | http://purl.uniprot.org/core/author | "Kivell B."xsd:string |
| http://purl.uniprot.org/citations/21653684 | http://purl.uniprot.org/core/author | "Gjyrezi A."xsd:string |
| http://purl.uniprot.org/citations/21653684 | http://purl.uniprot.org/core/author | "Escuin D."xsd:string |
| http://purl.uniprot.org/citations/21653684 | http://purl.uniprot.org/core/author | "Kanakkanthara A."xsd:string |
| http://purl.uniprot.org/citations/21653684 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21653684 | http://purl.uniprot.org/core/name | "Mol Cancer Ther"xsd:string |
| http://purl.uniprot.org/citations/21653684 | http://purl.uniprot.org/core/pages | "1419-1429"xsd:string |
| http://purl.uniprot.org/citations/21653684 | http://purl.uniprot.org/core/title | "Peloruside- and laulimalide-resistant human ovarian carcinoma cells have betaI-tubulin mutations and altered expression of betaII- and betaIII-tubulin isotypes."xsd:string |
| http://purl.uniprot.org/citations/21653684 | http://purl.uniprot.org/core/volume | "10"xsd:string |
| http://purl.uniprot.org/citations/21653684 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/21653684 |
| http://purl.uniprot.org/citations/21653684 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/21653684 |
| http://purl.uniprot.org/uniprot/#_Q1KSF8-mappedCitation-21653684 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21653684 |
| http://purl.uniprot.org/uniprot/#_A4UCU2-mappedCitation-21653684 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21653684 |