Cotranslational biogenesis of NF-kappaB p50 by the 26S proteasome.
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.
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Gladstone Institute of Virology and Immunology, Department of Microbiology and Immunology, University of California, San Francisco 94141, USA.
DeMartino
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Greene
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WC
D000818:Animals; D016466:CHO Cells / Q000737:chemistry / Q000201:enzymology; D006224:Cricetinae; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic; D005998:Glycine / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism*; D016296:Mutagenesis; D016328:NF-kappa B / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D014176:Protein Biosynthesis; D017510:Protein Folding; D011498:Protein Precursors / Q000378:metabolism
D009097:Multienzyme Complexes; D016328:NF-kappa B; D010446:Peptide Fragments; D011498:Protein Precursors; D005998:Glycine