COTRANSLATIONAL BIOGENESIS OF NF-KAPPA-B P50 BY THE 26S PROTEASOME

The NFKB1 gene encodes two functionally distinct proteins termed p50 a nd p105. p50 corresponds to the N terminus of p105 and with p65 (RelA) forms the prototypical NF-kappa B transcription factor complex. In co ntrast, p105 functions as a Rel-specific inhibitor (I kappa B) and has been proposed to be the precursor of p50. Our studies now demonstrate that p50 is generated by a unique cotranslational processing event in volving the 26S proteasome, whereas cotranslational folding of sequenc es near the C terminus of p50 abrogates proteasome processing acid lea ds to p105 production. These results indicate that p105 is not the pre cursor of p50 and reveal a novel mechanism of gene regulation that ens ures the balanced production and independent function of the p50 and p 105 proteins.