Chinese hamster ovary cells resistant to borrelidin overproduce threonyl-tRNA synthetase.
Chinese hamster ovary cell lines that are 1000-fold more resistant to the threonyl-tRNA synthetase inhibitor borrelidin than the sensitive parental cells were isolated after stepwise selection for growth in increasing concentrations of the drug. These cells show a 10-20-fold increase in threonyl-tRNA synthetase activity. Quantitation of the amount of threonyl-tRNA synthetase protein by immunological techniques indicated a 60-100-fold increase compared to sensitive cells. No significant changes in the Km for substrates, inhibition by borrelidin or thermal stability were found for the threonyl-tRNA synthetase of resistant cells. These data suggest that the resistant cell lines may have amplified the gene encoding threonyl-tRNA synthetase, but no evidence of homogeneously staining regions or double minute chromosomes was found. The resistant cell lines should prove useful for the study of the regulation of threonyl-tRNA synthetase.
D000604:Amino Acyl-tRNA Synthetases / Q000096:biosynthesis*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004351:Drug Resistance; D005233:Fatty Alcohols / Q000633:toxicity; D005260:Female; D007700:Kinetics; D010053:Ovary; D013914:Threonine-tRNA Ligase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D000900:Anti-Bacterial Agents; D005233:Fatty Alcohols; C005066:borrelidin; D000604:Amino Acyl-tRNA Synthetases; D013914:Threonine-tRNA Ligase