Matthew Naticchia - Bifunctional electrophiles cross-link thioredoxins with redox relay partners in cells

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      Publication Details (including relevant citation   information):

        Chem Res Toxicol.    2013 Mar 18;26(3):490-7. doi: 10.1021/tx4000123. Epub 2013 Mar   4

      Abstract:

        Thioredoxin protects cells against oxidative damage by reducing   disulfide bonds in improperly oxidized proteins. Previously, we   found that the baker's yeast cytosolic thioredoxin Trx2 undergoes   cross-linking to form several protein-protein complexes in cells   treated with the bifunctional electrophile divinyl sulfone   (DVSF). Here, we report that the peroxiredoxin Tsa1 and the   thioredoxin reductase Trr1, both of which function in a redox   relay network with thioredoxin, become cross-linked in complexes   with Trx2 upon DVSF treatment. Treatment of yeast with other   bifunctional electrophiles, including diethyl   acetylenedicarboxylate (DAD), mechlorethamine (HN2), and   1,2,3,4-diepoxybutane (DEB), resulted in the formation of similar   cross-linked complexes. Cross-linking of Trx2 and Tsa1 to other   proteins by DVSF and DAD is dependent on modification of the   active site Cys residues within these proteins. In addition, the   human cytosolic thioredoxin, cytosolic thioredoxin reductase, and   peroxiredoxin 2 form cross-linked complexes to other proteins in   the presence of DVSF, although each protein shows different   susceptibilities to modification by DAD, HN2, and DEB. Taken   together, our results indicate that bifunctional electrophiles   potentially disrupt redox homeostasis in yeast and human cells by   forming cross-linked complexes between thioredoxins and their   redox partners

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