Generation of NF-κB P50 from the NF-κB P105 precursor involves co-translational processing

The eukaryotic transcription factor NF KB corresponds to a heterodimer of p65 (RelA) and p50 subunits. The p5() subunit is derived from the N terminal portion of p 105, the product of the XF-Klil gene. Recent studies suggest that the generation of p50 from p 105 curiously involves targeted processing by the proteasorne. Further, a glycine.-rich region (GRR) within p 105 is required for the production of p50. Despite the presumed precursor-product relationship between the two proteins, we failed to observe chasing p 105 to pod either mvivoorin vitro. Rather, both proteins were simultaneously detected. Subsequent investigation indicated that the pl05 wa.s actually processed co translaùonally to generate p50 while still associated with the molecular chaperone Hsc.70 as a nascent chain. It seems likely that the GRR of p!05 is recog nized by some component of the proteasome leading to its co-translationally processing. In summary these data reveal a novel and unexpected mechanism for the generation of the pöO subunit of NF-KB that may be regulated by the stale of folding of the precursor p105.