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Coordinated dual cleavages induced by the proteasome regulator PA28 lead to dominant MHC ligands

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1996

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Dick, Tobias P.
Ruppert, Thomas
Kloetzel, Peter-Michael
Kühn, Lothar
Koszinowski, Ulrich
Stevanovic, Stefan
Schild, Hansjörg
Rammensee, Hans-Georg

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Cell. 1996, 86(2), pp. 253-262. ISSN 0092-8674. eISSN 1097-4172. Available under: doi: 10.1016/S0092-8674(00)80097-5

Zusammenfassung

The eukaryotic 20S proteasome is known to associate with the IFN gamma-inducible regulator PA28. We analyzed the kinetics of product generation by 20S proteasomes with and without PA28. In the absence of PA28, the 20S proteasome rapidly generates peptides that have been cleaved only once, while internal fragments accumulate only slowly. In the presence of PA28, products generated by two flanking cleavages appear immediately as main products while the generation of single-cleavage products is strongly reduced. Kinetic data support a PA28-induced, coordinated double-cleavage mechanism. In particular, degradation of peptides derived from mouse cytomegalovirus pp89 and JAK1 kinase in the presence of PA28 leads to strongly enhanced production of the respective major histocompatibility complex ligands and potential precursors. These results show that PA28 profoundly alters the cleavage mechanism of the proteasome and appears to optimize the generation of dominant T-cell epitopes.

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570 Biowissenschaften, Biologie

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ISO 690DICK, Tobias P., Thomas RUPPERT, Marcus GRÖTTRUP, Peter-Michael KLOETZEL, Lothar KÜHN, Ulrich KOSZINOWSKI, Stefan STEVANOVIC, Hansjörg SCHILD, Hans-Georg RAMMENSEE, 1996. Coordinated dual cleavages induced by the proteasome regulator PA28 lead to dominant MHC ligands. In: Cell. 1996, 86(2), pp. 253-262. ISSN 0092-8674. eISSN 1097-4172. Available under: doi: 10.1016/S0092-8674(00)80097-5
BibTex
@article{Dick1996Coord-22318,
  year={1996},
  doi={10.1016/S0092-8674(00)80097-5},
  title={Coordinated dual cleavages induced by the proteasome regulator PA28 lead to dominant MHC ligands},
  number={2},
  volume={86},
  issn={0092-8674},
  journal={Cell},
  pages={253--262},
  author={Dick, Tobias P. and Ruppert, Thomas and Gröttrup, Marcus and Kloetzel, Peter-Michael and Kühn, Lothar and Koszinowski, Ulrich and Stevanovic, Stefan and Schild, Hansjörg and Rammensee, Hans-Georg}
}
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