AP-1 DNA-binding activity is inhibited by selenite and selenodiglutathione.
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.
Spyrou
G
G
Medical Nobel Institute for Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Björnstedt
M
M
Kumar
S
S
Holmgren
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D004247:DNA / Q000378:metabolism*; D015342:DNA Probes; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011485:Protein Binding / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D018038:Sodium Selenite / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D015342:DNA Probes; D016566:Organoselenium Compounds; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; C017710:selenodiglutathione; D004247:DNA; D005978:Glutathione; D018038:Sodium Selenite