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PMID:10967121
| Citation |
Edwards, TK, Saleem, A, Shaman, JA, Dennis, T, Gerigk, C, Oliveros, E, Gartenberg, MR and Rubin, EH (2000) Role for nucleolin/Nsr1 in the cellular localization of topoisomerase I. J. Biol. Chem. 275:36181-8 |
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| Abstract |
Nucleolin functions in ribosome biogenesis and contains an acidic N terminus that binds nuclear localization sequences. In previous work we showed that human nucleolin associates with the N-terminal region of human topoisomerase I (Top1). We have now mapped the topoisomerase I interaction domain of nucleolin to the N-terminal 225 amino acids. We also show that the Saccharomyces cerevisiae nucleolin ortholog, Nsr1p, physically interacts with yeast topoisomerase I, yTop1p. Studies of isogenic NSR1(+) and Deltansr1 strains indicate that NSR1 is important in determining the cellular localization of yTop1p. Moreover, deletion of NSR1 reduces sensitivity to camptothecin, an antineoplastic topoisomerase I inhibitor. By contrast, Deltansr1 cells are hypersensitive to the topoisomerase II-targeting drug amsacrine. These findings indicate that nucleolin/Nsr1 is involved in the cellular localization of Top1 and that this localization may be important in determining sensitivity to drugs that target topoisomerases. |
| Links |
PubMed Online version:10.1074/jbc.M006628200 |
| Keywords |
Amsacrine/pharmacology; Antineoplastic Agents/pharmacology; Camptothecin/pharmacology; Cell Division/genetics; DNA Topoisomerases, Type I/metabolism; DNA Topoisomerases, Type II/metabolism; Drug Resistance, Microbial/genetics; Fungal Proteins/chemistry; Fungal Proteins/genetics; Fungal Proteins/metabolism; Humans; Microbial Sensitivity Tests; Microscopy, Fluorescence; Mutation; Nuclear Proteins; Protein Binding; Protein Structure, Tertiary; Protein Transport; RNA-Binding Proteins; Recombinant Fusion Proteins/metabolism; Saccharomyces cerevisiae/enzymology; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins; Subcellular Fractions/chemistry; Topoisomerase I Inhibitors; Topoisomerase II Inhibitors; Transformation, Genetic |
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Significance
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