Ref-1 controls pax-8 DNA-binding activity.
Redox potential controls the DNA-binding activity of several transcription factors. In some cases, the regulation of DNA-binding activity by the redox state is mediated by the Ref-1 nuclear protein. In this study, we demonstrate that Ref-1 is able to induce "in vitro" the DNA-binding activity of the Pax-8 paired domain. In co-transfection experiments, Ref-1 increases the Pax-8 activating effect on thyroglobulin promoter. Moreover, immunoreactivity data suggest that, in nuclear extracts of thyroid cells, the levels of Ref-1 correlate with the amounts of reduced Pax-8. Therefore, the regulation of the Pax-8 DNA-binding activity by redox potential, that we have demonstrated occurring "in vitro", could represent a means to control "in vivo" the function of Pax proteins. Alignment of the Paired domains sequences present in the Protein Data Bank demonstrates a strong conservation of Cys residues, suggesting that the redox regulation of the Paired domain DNA-binding activity is widely conserved along phylogenesis.
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Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi di Udine, via Gervasutta 48, Udine, 33100, Italy. immunoud@dstb.uniud.it
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D000595:Amino Acid Sequence; D000818:Animals; D019757:Carbon-Oxygen Lyases / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013954:Thyroglobulin / Q000235:genetics*; D013961:Thyroid Gland / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry* / Q000378:metabolism*; D014162:Transfection
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D011994:Recombinant Proteins; D015534:Trans-Activators; D013954:Thyroglobulin; D004720:Endonucleases; D019757:Carbon-Oxygen Lyases; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase