L. Lin et al., Cotranslational dimerization of the Rel homology domain of NF-kappa B1 generates p50-p105 heterodimers and is required for effective p50 production, EMBO J, 19(17), 2000, pp. 4712-4722
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.