PMID:7615089

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Citation

Spyrou, G, Björnstedt, M, Kumar, S and Holmgren, A (1995) AP-1 DNA-binding activity is inhibited by selenite and selenodiglutathione. FEBS Lett. 368:59-63

Abstract

The binding of the transcription factor AP-1 to DNA has been shown to be modulated by redox control mechanisms. Selenite and selenodiglutathione (GS-Se-SG), inhibit mammalian cell growth and are efficient oxidants of reduced thioredoxin and reduced thioredoxin reductase. Here, we report that selenite and GS-Se-SG efficiently inhibited AP-1 DNA-binding in nuclear extracts from 3B6 lymphocytes. A GS-Se-SG concentration of 0.75 microM resulted in 50% inhibition of AP-1 DNA-binding, whereas the same effect was achieved with 7.5 microM selenite. Nuclear extracts prepared from human 3B6 lymphocytes exposed for 4 h to 10 microM selenite showed a 50% reduction of AP-1 binding. These data suggest that selenite and selenodiglutathione inactivate the AP-1 factor and provide a mechanism by which selenium compounds inhibit cell growth.

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Keywords

Amino Acid Sequence; Animals; Base Sequence; Cell Division/drug effects; Cell Line, Transformed; DNA/metabolism; DNA Probes; Glutathione/analogs & derivatives; Glutathione/pharmacology; Humans; Lymphocytes/metabolism; Mice; Molecular Sequence Data; Organoselenium Compounds/pharmacology; Oxidation-Reduction; Protein Binding/drug effects; Proto-Oncogene Proteins c-fos/metabolism; Proto-Oncogene Proteins c-jun/metabolism; Sodium Selenite/pharmacology; Transcription Factor AP-1/metabolism

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