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

Author

Listed:
  • Ulrich Schubert

    (Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases
    Heinrich-Pette Institute, University of Hamburg)

  • Luis C. Antón

    (Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases)

  • James Gibbs

    (Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases)

  • Christopher C. Norbury

    (Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases)

  • Jonathan W. Yewdell

    (Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases)

  • Jack R. Bennink

    (Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases)

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.

Suggested Citation

  • Ulrich Schubert & Luis C. Antón & James Gibbs & Christopher C. Norbury & Jonathan W. Yewdell & Jack R. Bennink, 2000. "Rapid degradation of a large fraction of newly synthesized proteins by proteasomes," Nature, Nature, vol. 404(6779), pages 770-774, April.
  • Handle: RePEc:nat:nature:v:404:y:2000:i:6779:d:10.1038_35008096
    DOI: 10.1038/35008096
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    Cited by:

    1. Feiran Li & Yu Chen & Qi Qi & Yanyan Wang & Le Yuan & Mingtao Huang & Ibrahim E. Elsemman & Amir Feizi & Eduard J. Kerkhoven & Jens Nielsen, 2022. "Improving recombinant protein production by yeast through genome-scale modeling using proteome constraints," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Fredrik Trulsson & Vyacheslav Akimov & Mihaela Robu & Nila Overbeek & David Aureliano Pérez Berrocal & Rashmi G. Shah & Jürgen Cox & Girish M. Shah & Blagoy Blagoev & Alfred C. O. Vertegaal, 2022. "Deubiquitinating enzymes and the proteasome regulate preferential sets of ubiquitin substrates," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Bayan Mashahreh & Shir Armony & Kristoffer Enøe Johansson & Alon Chappleboim & Nir Friedman & Richard G. Gardner & Rasmus Hartmann-Petersen & Kresten Lindorff-Larsen & Tommer Ravid, 2022. "Conserved degronome features governing quality control associated proteolysis," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    4. Narasaiah Kovuru & Makiko Mochizuki-Kashio & Theresa Menna & Greer Jeffrey & Yuning Hong & Young me Yoon & Zhe Zhang & Peter Kurre, 2024. "Deregulated protein homeostasis constrains fetal hematopoietic stem cell pool expansion in Fanconi anemia," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    5. Daniel A. Nissley & Yang Jiang & Fabio Trovato & Ian Sitarik & Karthik B. Narayan & Philip To & Yingzi Xia & Stephen D. Fried & Edward P. O’Brien, 2022. "Universal protein misfolding intermediates can bypass the proteostasis network and remain soluble and less functional," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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