Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro erythroid differentiation of mouse erythroleukemia (MEL) cells was induced by combinations of topoisomerase and protein kinase inhibitors. Neither inhibitor alone exhibited inducing activity. Although inhibitors of topoisomerases I and II were equally effective in the synergistic induction of erythroid differentiation, only inhibitors of tyrosine kinases, not of serine/threonine kinases, exhibited synergistic activity. The erythroid differentiation induced by the combination of topoisomerase and protein tyrosine kinase inhibitors was distinguished from that induced by typical erythroid inducing agents such as DMSO or HMBA by (1) earlier hemoglobin accumulation in the cells and (2) insensitivity to specific inhibitors (dexamethasone and sodium orthovanadate) of MEL cell differentiation.
 ...
PMID:Synergistic induction of erythroid differentiation of mouse erythroleukemia (MEL) cells by inhibitors of topoisomerases and protein tyrosine kinases. 131 8

DNA topoisomerase II has been shown to be a nuclear marker for cell proliferation and a therapeutic target in cancer chemotherapy. In order to study the regulation of DNA topoisomerases during cellular differentiation, MELC were induced to differentiate by treatment with 5 mM HMBA. At day five, approximately 95% of MELC had reproducibly undergone differentiation. The level of topoisomerase II, as measured by immunoblotting with anti-topoisomerase II antisera, showed a parallel decrease to approximately 5-10% of the control level by day five. Activity measurements showed a similar decrease during the time course of MELC differentiation. Immunofluorescence studies at day five showed that only about 5% of the MELC had strong nuclear immunofluorescence. These results indicate that the level and activity of DNA topoisomerase II are significantly lower in differentiated versus undifferentiated cells. We also observed that the level and activity of topoisomerase II dropped twofold as cells grew to high cell densities in the absence of HMBA. In contrast, the topoisomerase I levels in MELC remained relatively constant throughout growth and differentiation.
 ...
PMID:Regulation of DNA topoisomerases during cellular differentiation. 281 28