Discrete Cleavage Motifs of Constitutive and Immunoproteasomes Revealed by Quantitative Analysis of Cleavage Products
10.1084/jem.194.1.1
Crossref journal-article
Rockefeller University Press
The Journal of Experimental Medicine (291)
Abstract

Proteasomes are the main proteases responsible for cytosolic protein degradation and the production of major histocompatibility complex class I ligands. Incorporation of the interferon γ–inducible subunits low molecular weight protein (LMP)-2, LMP-7, and multicatalytic endopeptidase complex–like (MECL)-1 leads to the formation of immunoproteasomes which have been associated with more efficient class I antigen processing. Although differences in cleavage specificities of constitutive and immunoproteasomes have been observed frequently, cleavage motifs have not been described previously. We now report that cells expressing immunoproteasomes display a different peptide repertoire changing the overall cytotoxic T cell–specificity as indicated by the observation that LMP-7−/− mice react against cells of LMP-7 wild-type mice. Moreover, using the 436 amino acid protein enolase-1 as an unmodified model substrate in combination with a quantitative approach, we analyzed a large collection of peptides generated by either set of proteasomes. Inspection of the amino acids flanking proteasomal cleavage sites allowed the description of two different cleavage motifs. These motifs finally explain recent findings describing differential processing of epitopes by constitutive and immunoproteasomes and are important to the understanding of peripheral T cell tolerization/activation as well as for effective vaccine development.

Bibliography

Toes, R. E. M., Nussbaum, A. K., Degermann, S., Schirle, M., Emmerich, N. P. N., Kraft, M., Laplace, C., Zwinderman, A., Dick, T. P., Müller, J., Schönfisch, B., Schmid, C., Fehling, H.-J., Stevanovic, S., Rammensee, H. G., & Schild, H. (2001). Discrete Cleavage Motifs of Constitutive and Immunoproteasomes Revealed by Quantitative Analysis of Cleavage Products. The Journal of Experimental Medicine, 194(1), 1–12.

Authors 16
  1. R.E.M. Toes (first)
  2. A.K. Nussbaum (additional)
  3. S. Degermann (additional)
  4. M. Schirle (additional)
  5. N.P.N. Emmerich (additional)
  6. M. Kraft (additional)
  7. C. Laplace (additional)
  8. A. Zwinderman (additional)
  9. T.P. Dick (additional)
  10. J. Müller (additional)
  11. B. Schönfisch (additional)
  12. C. Schmid (additional)
  13. H.-J. Fehling (additional)
  14. S. Stevanovic (additional)
  15. H.G. Rammensee (additional)
  16. H. Schild (additional)
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Dates
Type When
Created 23 years, 1 month ago (July 26, 2002, 12:48 p.m.)
Deposited 2 years, 1 month ago (July 25, 2023, 6:55 a.m.)
Indexed 1 week ago (Aug. 21, 2025, 2:17 p.m.)
Issued 24 years, 2 months ago (June 25, 2001)
Published 24 years, 2 months ago (June 25, 2001)
Published Online 24 years, 2 months ago (June 25, 2001)
Published Print 24 years, 1 month ago (July 2, 2001)
Funders 0

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@article{Toes_2001, title={Discrete Cleavage Motifs of Constitutive and Immunoproteasomes Revealed by Quantitative Analysis of Cleavage Products}, volume={194}, ISSN={1540-9538}, url={http://dx.doi.org/10.1084/jem.194.1.1}, DOI={10.1084/jem.194.1.1}, number={1}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Toes, R.E.M. and Nussbaum, A.K. and Degermann, S. and Schirle, M. and Emmerich, N.P.N. and Kraft, M. and Laplace, C. and Zwinderman, A. and Dick, T.P. and Müller, J. and Schönfisch, B. and Schmid, C. and Fehling, H.-J. and Stevanovic, S. and Rammensee, H.G. and Schild, H.}, year={2001}, month=jun, pages={1–12} }