Epidermal growth factor-induced topoisomerase(s). Intracellular translocation and relation to DNA synthesis.
We have used epidermal growth factor (EGF) to investigate the relationship between eukaryotic topoisomerases and DNA synthesis. We found that EGF stimulates topoisomerase activity in human fibroblasts and Swiss/3T3 mouse fibroblasts. The first increase is seen in the cytoplasm, followed by increased activity in the nucleus. The nuclear increases correspond to increases in DNA synthesis. A type II topoisomerase is stimulated as indicated by the ATP dependence of the relaxing reaction and by the formation of catenanes. We have also found that the topoisomerase activity in the cytoplasm is sedimentable indicating that it is either membrane-associated or in a supramolecular complex. The stimulation of topoisomerase activity by EGF may represent a key step in the process by which EGF induces DNA synthesis and cell division.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects*; D004264:DNA Topoisomerases, Type I / Q000096:biosynthesis*; D004790:Enzyme Induction; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D051379:Mice
D004815:Epidermal Growth Factor; D000255:Adenosine Triphosphate; D004264:DNA Topoisomerases, Type I