Ref-1 controls pax-8 DNA-binding activity

Biochem Biophys Res Commun. 1998 Nov 9;252(1):178-83. doi: 10.1006/bbrc.1998.9548.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carbon-Oxygen Lyases / metabolism*
  • Cell Nucleus / metabolism
  • DNA Repair
  • DNA-(Apurinic or Apyrimidinic Site) Lyase*
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism*
  • Endonucleases / metabolism*
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism
  • PAX8 Transcription Factor
  • Paired Box Transcription Factors
  • Promoter Regions, Genetic
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Thyroglobulin / genetics*
  • Thyroid Gland / metabolism
  • Trans-Activators / chemistry*
  • Trans-Activators / metabolism*
  • Transfection

Substances

  • DNA-Binding Proteins
  • Nuclear Proteins
  • PAX8 Transcription Factor
  • PAX8 protein, human
  • Paired Box Transcription Factors
  • Recombinant Proteins
  • Trans-Activators
  • Thyroglobulin
  • Endonucleases
  • Carbon-Oxygen Lyases
  • APEX1 protein, human
  • DNA-(Apurinic or Apyrimidinic Site) Lyase