Two isoforms of protein disulfide isomerase alter the dimerization status of E2A proteins by a redox mechanism.

We have shown previously that E2A helix-loop-helix proteins spontaneously form an intermolecular disulfide cross-link that is required for stable homodimer binding to DNA (Benezra, R. (1994) Cell 79, 1057-1067). These homodimers are important for the development of B lymphocytes but are not present in other cell lineages. We have purified two proteins that are capable of regulating the formation of this disulfide bond and found them to be members of the protein disulfide isomerase (PDI) family. By regulating the formation of the disulfide cross-link, these proteins are capable of regulating the dimerization state of E proteins. PDI-mediated reduction appears to dissociate E protein homodimers and favors heterodimer formation with other basic helix-loop-helix proteins in both a purified protein system and in cellular extracts. These studies suggest that PDI may play an important role in the regulation of E2A transcription factor dimerization and the development of the B lymphocyte lineage.