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http://purl.uniprot.org/citations/7882333http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/7882333http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/7882333http://www.w3.org/2000/01/rdf-schema#comment"We developed previously a resistant cell line, CEM/C2, from the human leukemia cell line CCRF-CEM by stepwise selection in camptothecin. This cell line is 974-fold more resistant to camptothecin than parental cells. Resistance is only partially explained by 2-fold reductions in topoisomerase I protein and mRNA levels. We further investigated biochemical and molecular features of topoisomerase I in the resistant cell line. Sequence analyses of the top1 cDNA from CEM/C2 identified mutations corresponding to two amino acid substitutions, Met370Thr and Asn722Ser. Asn722Ser is next to the catalytic Tyr723 in a region highly conserved among type I eukaryotic DNA topoisomerases. Recombinant top1 with the corresponding substitution was found to be catalytically active and resistant to camptothecin. These results indicate that camptothecin resistance of CEM/C2 is due to the mutation Asn722Ser and strongly suggest that the asparagine immediately flanking the catalytic tyrosine is important for the camptothecin action."xsd:string
http://purl.uniprot.org/citations/7882333http://purl.uniprot.org/core/author"Pommier Y."xsd:string
http://purl.uniprot.org/citations/7882333http://purl.uniprot.org/core/author"Pommier Y."xsd:string
http://purl.uniprot.org/citations/7882333http://purl.uniprot.org/core/author"Fujimori A."xsd:string
http://purl.uniprot.org/citations/7882333http://purl.uniprot.org/core/author"Fujimori A."xsd:string
http://purl.uniprot.org/citations/7882333http://purl.uniprot.org/core/author"Kohlhagen G."xsd:string
http://purl.uniprot.org/citations/7882333http://purl.uniprot.org/core/author"Kohlhagen G."xsd:string
http://purl.uniprot.org/citations/7882333http://purl.uniprot.org/core/author"Hoki Y."xsd:string
http://purl.uniprot.org/citations/7882333http://purl.uniprot.org/core/author"Hoki Y."xsd:string
http://purl.uniprot.org/citations/7882333http://purl.uniprot.org/core/author"Harker W.G."xsd:string
http://purl.uniprot.org/citations/7882333http://purl.uniprot.org/core/author"Harker W.G."xsd:string
http://purl.uniprot.org/citations/7882333http://purl.uniprot.org/core/date"1995"xsd:gYear
http://purl.uniprot.org/citations/7882333http://purl.uniprot.org/core/date"1995"xsd:gYear
http://purl.uniprot.org/citations/7882333http://purl.uniprot.org/core/name"Cancer Res."xsd:string
http://purl.uniprot.org/citations/7882333http://purl.uniprot.org/core/name"Cancer Res."xsd:string
http://purl.uniprot.org/citations/7882333http://purl.uniprot.org/core/pages"1339-1346"xsd:string
http://purl.uniprot.org/citations/7882333http://purl.uniprot.org/core/pages"1339-1346"xsd:string
http://purl.uniprot.org/citations/7882333http://purl.uniprot.org/core/title"Mutation at the catalytic site of topoisomerase I in CEM/C2, a human leukemia cell line resistant to camptothecin."xsd:string
http://purl.uniprot.org/citations/7882333http://purl.uniprot.org/core/title"Mutation at the catalytic site of topoisomerase I in CEM/C2, a human leukemia cell line resistant to camptothecin."xsd:string
http://purl.uniprot.org/citations/7882333http://purl.uniprot.org/core/volume"55"xsd:string
http://purl.uniprot.org/citations/7882333http://purl.uniprot.org/core/volume"55"xsd:string
http://purl.uniprot.org/citations/7882333http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/7882333
http://purl.uniprot.org/citations/7882333http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/7882333