Redox regulation of fos and jun DNA-binding activity in vitro.
The proto-oncogenes c-fos and c-jun function cooperatively as inducible transcription factors in signal transduction processes. Their protein products, Fos and Jun, form a heterodimeric complex that interacts with the DNA regulatory element known as the activator protein-1 (AP-1) binding site. Dimerization occurs via interaction between leucine zipper domains and serves to bring into proper juxtaposition a region in each protein that is rich in basic amino acids and that forms a DNA-binding domain. DNA binding of the Fos-Jun heterodimer was modulated by reduction-oxidation (redox) of a single conserved cysteine residue in the DNA-binding domains of the two proteins. Furthermore, a nuclear protein was identified that reduced Fos and Jun and stimulated DNA-binding activity in vitro. These results suggest that transcriptional activity mediated by AP-1 binding factors may be regulated by a redox mechanism.
Abate
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Department of Molecular Oncology and Virology, Roche Institute of Molecular Biology, Nutley, NJ 07110.
Patel
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L
Rauscher
F J
FJ
Curran
T
T
D000595:Amino Acid Sequence; D000818:Animals; D002474:Cell-Free System; D003545:Cysteine / Q000502:physiology; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000502:physiology*; D003958:Diamide / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D051381:Rats; D011994:Recombinant Proteins; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D014157:Transcription Factors / Q000502:physiology*
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011994:Recombinant Proteins; D013439:Sulfhydryl Reagents; D014157:Transcription Factors; D003958:Diamide; D003545:Cysteine