Cotranslational biogenesis of NF-kappaB p50 by the 26S proteasome

Cell. 1998 Mar 20;92(6):819-28. doi: 10.1016/s0092-8674(00)81409-9.


The NFkappaB1 gene encodes two functionally distinct proteins termed p50 and p105. p50 corresponds to the N terminus of p105 and with p65 (RelA) forms the prototypical NF-kappaB transcription factor complex. In contrast, p105 functions as a Rel-specific inhibitor (IKB) and has been proposed to be the precursor of p50. Our studies now demonstrate that p50 is generated by a unique cotranslational processing event involving the 26S proteasome, whereas cotranslational folding of sequences near the C terminus of p50 abrogates proteasome processing and leads to p105 production. These results indicate that p105 is not the precursor of p50 and reveal a novel mechanism of gene regulation that ensures the balanced production and independent function of the p50 and p105 proteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CHO Cells / chemistry
  • CHO Cells / enzymology
  • Cricetinae
  • Gene Deletion
  • Gene Expression Regulation, Enzymologic
  • Glycine / metabolism
  • Multienzyme Complexes / metabolism*
  • Mutagenesis
  • NF-kappa B / chemistry
  • NF-kappa B / genetics*
  • NF-kappa B / metabolism*
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Protein Biosynthesis
  • Protein Folding
  • Protein Precursors / metabolism


  • Multienzyme Complexes
  • NF-kappa B
  • Peptide Fragments
  • Protein Precursors
  • Glycine