Abstract
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 proteasomes1, and are transported into the endoplasmic reticulum, where they assemble with nascent class I molecules2. 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 folding3. 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.
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Acknowledgements
We thank B. Buschling for technical assistance. C.N. is the recipient of a Wellcome Prize Traveling Fellowship; U.S. was supported by grant Schu11/2-1 and a Heisenberg grant from the Deutsche Forschungsgemeinschaft.
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Schubert, U., Antón, L., Gibbs, J. et al. Rapid degradation of a large fraction of newly synthesized proteins by proteasomes. Nature 404, 770–774 (2000). https://doi.org/10.1038/35008096
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DOI: https://doi.org/10.1038/35008096
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