REF-1 CONTROLS PAX-8 DNA-BINDING ACTIVITY

Redox potential controls the DNA-binding activity of several transcrip tion factors. In some cases, the regulation of DNA-binding activity by the redox state is mediated by the Ref-1 nuclear protein. In this stu dy, we demonstrate that Ref-1 is able to induce ''in vitro'' the DNA-b inding activity of the Pax-8 paired domain. In cotransfection experime nts, Ref-1 increases the Pax-8 activating effect on thyroglobulin prom oter, Moreover, immunoreactivity data suggest that, in nuclear extract s 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 acti vity by redox potential, that we have demonstrated occurring ''in vitr o'', could represent a means to control ''in vivo'' the function of Pa x proteins. Alignment of the Paired domains sequences present in the P rotein Data Bank demonstrates a strong conservation of Cys residues, s uggesting that the redox regulation of the Paired domain DNA-binding a ctivity is widely conserved along phylogenesis. (C) 1998 Academic Pres s.