Two different cellular redox systems regulate the DNA-binding activity of the p50 subunit of NF-kappa B in vitro.
The NF-kappa B/Rel/Dorsal (NRD) transcription factor family binds target DNA sequences through their conserved N-terminal basic region that contains a single cysteine residue flanked by basic residues. This cysteine residue plays a critical role in the regulation of the DNA-binding activity of NRD members, since chemical modifications of this residue modulate the DNA-binding activity of NRD members. Here we show that cellular factors regulate the DNA-binding activity of NRD members in vitro by reduction-oxidation (redox) mechanisms. Two cellular redox systems, thioredoxin/thioredoxin reductase and apurinic/apyrimidinic endonuclease (also called Redox factor-1), independently, as well as, synergistically stimulate the DNA-binding activity of bacterially synthesized (recombinant) p50, one of the subunits of NF-kappa B that is a major NRD factor inducible in various types of cells. Since the mutation of the conserved residue (Cys61) in the N-terminal basic region of p50 impairs the stimulation of p50 DNA-binding activity by these redox factors, the regulation of p50 DNA-binding activity by these redox factors is mediated through this cysteine residue. It is, therefore, possible that these two cellular redox systems could play independent, as well as synergistic roles in the regulation of NF-kappa B functions in vivo through the redox control of their DNA-binding activity.
Mitomo
K
K
Department of Molecular Pathology, Cancer Research Institute, Kanazawa University, Ishikawa, Japan.
Nakayama
K
K
Fujimoto
K
K
Sun
X
X
Seki
S
S
Yamamoto
K
K
D000595:Amino Acid Sequence; D001483:Base Sequence; D019757:Carbon-Oxygen Lyases; D004247:DNA / Q000378:metabolism*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010084:Oxidation-Reduction; D011485:Protein Binding; D011487:Protein Conformation; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020569:Proto-Oncogene Proteins c-rel; D013329:Structure-Activity Relationship; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism
D016328:NF-kappa B; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D013879:Thioredoxins; D004247:DNA; D013880:Thioredoxin-Disulfide Reductase; D019757:Carbon-Oxygen Lyases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase