Rapid degradation of a large fraction of newly synthesized proteins by proteasomes

Nature. 2000 Apr 13;404(6779):770-4. doi: 10.1038/35008096.


MHC class I molecules function to present peptides eight to ten residues long to the immune system. These peptides originate primarily from a cytosolic pool of proteins through the actions of proteasomes, and are transported into the endoplasmic reticulum, where they assemble with nascent class I molecules. Most peptides are generated from proteins that are apparently metabolically stable. To explain this, we previously proposed that peptides arise from proteasomal degradation of defective ribosomal products (DRiPs). DRiPs are polypeptides that never attain native structure owing to errors in translation or post-translational processes necessary for proper protein folding. Here we show, first, that DRiPs constitute upwards of 30% of newly synthesized proteins as determined in a variety of cell types; second, that at least some DRiPs represent ubiquitinated proteins; and last, that ubiquitinated DRiPs are formed from human immunodeficiency virus Gag polyprotein, a long-lived viral protein that serves as a source of antigenic peptides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cysteine Endopeptidases / metabolism*
  • Cysteine Proteinase Inhibitors / pharmacology
  • Dendritic Cells / metabolism
  • Gene Products, gag / metabolism
  • HeLa Cells
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Leupeptins / pharmacology
  • Mice
  • Multienzyme Complexes / metabolism*
  • Peptide Biosynthesis
  • Proteasome Endopeptidase Complex
  • Protein Biosynthesis
  • Protein Precursors / biosynthesis
  • Protein Precursors / metabolism*
  • Proteins / chemistry
  • Proteins / metabolism*
  • Ubiquitins / metabolism


  • Cysteine Proteinase Inhibitors
  • Gene Products, gag
  • Histocompatibility Antigens Class I
  • Leupeptins
  • Multienzyme Complexes
  • Protein Precursors
  • Proteins
  • Ubiquitins
  • p55 gag precursor protein, Human immunodeficiency virus 1
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde