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 f orm an intermolecular disulfide cross-link that is required for stable homo dimer binding to DNA (Benezra, R. (1994) Cell 79, 1057-1067). These homodim ers 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 r egulating the formation of this disulfide bond and found them to be members of the protein disulfide isomerase (PDI) family. By regulating the formati on of the disulfide cross-link, these proteins are capable of regulating th e dimerization state of E proteins. PDI-mediated reduction appears to disso ciate E protein homodimers and favors heterodimer formation with other basi c helix-loop-helix proteins in both a purified protein system and in cellul ar extracts. These studies suggest that PDI may play an important role in t he regulation of E2A transcription factor dimerization and the development of the B lymphocyte lineage.