A protein factor that enhances amsacrine-mediated formation of topoisomerase II-DNA complexes in murine mastocytoma cell nuclei.
Extracts of K21 murine mastocytoma cells contain a factor that enhances formation of amsacrine-induced topoisomerase II-DNA complexes (PDCs) when added to isolated K21 nuclei. The PDC-enhancing activity is reduced in extracts from 2 or 6 h cycloheximide or cordycepin-treated cells, implying that continuous protein synthesis is required to maintain the factor. The factor is heat-labile, proteinase-sensitive and has other properties that distinguish it from the two known classes of topoisomerases. The data suggest that the factor is a labile protein with a molecular weight in excess of 50,000. This appears to be the first direct evidence of a protein factor that modulates drug-induced topoisomerase II action.
Darkin
S J
SJ
Department of Cellular and Molecular Biology, University of Auckland, New Zealand.
Ralph
R K
RK
D000677:Amsacrine / Q000494:pharmacology*; D000818:Animals; D002467:Cell Nucleus / Q000502:physiology; D002474:Cell-Free System; D003593:Cytoplasm / Q000502:physiology; D004273:DNA, Neoplasm / Q000378:metabolism*; D006358:Hot Temperature; D046911:Macromolecular Substances; D012515:Mast-Cell Sarcoma / Q000503:physiopathology*; D051379:Mice; D010447:Peptide Hydrolases / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D059005:Topoisomerase II Inhibitors
D004273:DNA, Neoplasm; D046911:Macromolecular Substances; D059005:Topoisomerase II Inhibitors; D000677:Amsacrine; D010447:Peptide Hydrolases