Michael Mattern

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Merbarone has previously been shown to have antitumor activity of unknown mechanism in P38S and 1,1210 tumor models (A. D. Brewer et a/., Biochem. Pharmacol., 34:2047-2050,1985) and is currently undergo ing Phase I clinical trials. Here we report that merbarone is an inhibitor of topoisomerase II. Merbarone inhibited purified mammalian topoisom-erase II(More)
DMA intercalating drugs and the epipodophyllotoxins etopo-side and teniposide interfere with the action of mammalian DNA topoisomerase II by trapping an intermediate complex of the enzyme covalently linked to the 5'-termini of DNA breaks. This effect can be observed in intact cells by alkaline elution mea surement of protein-associated DNA strand breaks. To(More)
The ubiquitin pathway regulates diverse functions including protein localization and stability. The complexity of the pathway involving nearly 40 identified E2 conjugating enzymes and over 600 E3 ligases raises the issue of specificity. With the E2s and E3s fitting into a limited number of classes based on bioinformatics, structures, and proven activities,(More)
A combination of tumor necrosis factor (INI) and the topoisomerase I inhibitor, camptothecin, or the topoisomerase II inhibitors, teniposide and amsacrine, produced dose-dependent synergistic cytotoxicity against the murine L929 fibrosarcoma cells. Similar synergy was not observed with a combination of TNF and bleomycin. To define the role of TNF in the(More)
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