Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/19744312http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19744312http://www.w3.org/2000/01/rdf-schema#comment"

Background

Nitrogen-containing bisphosphonates are the elected drugs for the treatment of diseases in which excessive bone resorption occurs, for example, osteoporosis and cancer-induced bone diseases. The only known target of nitrogen-containing bisphosphonates is farnesyl pyrophosphate synthase, which ensures prenylation of prosurvival proteins, such as Ras. However, it is likely that the action of nitrogen-containing bisphosphonates involves additional unknown mechanisms. To identify novel targets of nitrogen-containing bisphosphonates, we used a genome-wide high-throughput screening in which 5,936 Saccharomyces cerevisiae heterozygote barcoded mutants were grown competitively in the presence of sub-lethal doses of three nitrogen-containing bisphosphonates (risedronate, alendronate and ibandronate). Strains carrying deletions in genes encoding potential drug targets show a variation of the intensity of their corresponding barcodes on the hybridization array over the time.

Results

With this approach, we identified novel targets of nitrogen-containing bisphosphonates, such as tubulin cofactor B and ASK/DBF4 (Activator of S-phase kinase). The up-regulation of tubulin cofactor B may explain some previously unknown effects of nitrogen-containing bisphosphonates on microtubule dynamics and organization. As nitrogen-containing bisphosphonates induce extensive DNA damage, we also document the role of DBF4 as a key player in nitrogen-containing bisphosphonate-induced cytotoxicity, thus explaining the effects on the cell-cycle.

Conclusions

The dataset obtained from the yeast screen was validated in a mammalian system, allowing the discovery of new biological processes involved in the cellular response to nitrogen-containing bisphosphonates and opening up opportunities for development of new anticancer drugs."xsd:string
http://purl.uniprot.org/citations/19744312http://purl.org/dc/terms/identifier"doi:10.1186/gb-2009-10-9-r93"xsd:string
http://purl.uniprot.org/citations/19744312http://purl.uniprot.org/core/author"Harrison R."xsd:string
http://purl.uniprot.org/citations/19744312http://purl.uniprot.org/core/author"Delneri D."xsd:string
http://purl.uniprot.org/citations/19744312http://purl.uniprot.org/core/author"Moro L."xsd:string
http://purl.uniprot.org/citations/19744312http://purl.uniprot.org/core/author"Tell G."xsd:string
http://purl.uniprot.org/citations/19744312http://purl.uniprot.org/core/author"Quadrifoglio F."xsd:string
http://purl.uniprot.org/citations/19744312http://purl.uniprot.org/core/author"Romanello M."xsd:string
http://purl.uniprot.org/citations/19744312http://purl.uniprot.org/core/author"Hoyle D.C."xsd:string
http://purl.uniprot.org/citations/19744312http://purl.uniprot.org/core/author"Clarke I."xsd:string
http://purl.uniprot.org/citations/19744312http://purl.uniprot.org/core/author"Bonetti A."xsd:string
http://purl.uniprot.org/citations/19744312http://purl.uniprot.org/core/author"Bivi N."xsd:string
http://purl.uniprot.org/citations/19744312http://purl.uniprot.org/core/author"Ortolani F."xsd:string
http://purl.uniprot.org/citations/19744312http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19744312http://purl.uniprot.org/core/name"Genome Biol"xsd:string
http://purl.uniprot.org/citations/19744312http://purl.uniprot.org/core/pages"R93"xsd:string
http://purl.uniprot.org/citations/19744312http://purl.uniprot.org/core/title"Identification of secondary targets of N-containing bisphosphonates in mammalian cells via parallel competition analysis of the barcoded yeast deletion collection."xsd:string
http://purl.uniprot.org/citations/19744312http://purl.uniprot.org/core/volume"10"xsd:string
http://purl.uniprot.org/citations/19744312http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/19744312
http://purl.uniprot.org/citations/19744312http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/19744312
http://purl.uniprot.org/uniprot/#_P11076-mappedCitation-19744312http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19744312
http://purl.uniprot.org/uniprot/#_P53867-mappedCitation-19744312http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19744312
http://purl.uniprot.org/uniprot/#_P53904-mappedCitation-19744312http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19744312
http://purl.uniprot.org/uniprot/#_A0A8H8UMX1-mappedCitation-19744312http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19744312
▶