Cotranslational dimerization of the Rel homology domain of NF-kappa B1 generates p50-p105 heterodimers and is required for effective p50 production

Generation of the NF-kappa B p50 transcription factor is mediated by the pr oteasome, We found previously that p50 is generated during translation of t he NFKB1 gene and that this cotranslational processing allows the productio n of both p50 and p105 from a single mRNA. We now demonstrate that the Rel homology domain in p50 undergoes cotranslational dimerization and that this interaction is required for efficient production of p50. We further show t hat this coupling of dimerization and proteasome processing during translat ion uniquely generates p50-p105 heterodimers. Accordingly, after the primar y cotranslational event, additional posttranslational steps regulate p50 ho modimer formation and the intracellular ratio of p50 and p105. This cellula r strategy places p50 under the control of the p105 inhibitor early in its biogenesis, thereby regulating the pool of p50 homodimers within the cell.