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The 20S Proteasome Splicing Activity Discovered by SpliceMet

The identification of proteasome-generated spliced peptides (PSP) revealed a new unpredicted activity of the major cellular protease. However, so far characterization of PSP was entirely dependent on the availability of patient-derived cytotoxic CD8+ T lymphocytes (CTL) thus preventing a systematic...

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Autores principales: Liepe, Juliane, Mishto, Michele, Textoris-Taube, Kathrin, Janek, Katharina, Keller, Christin, Henklein, Petra, Kloetzel, Peter Michael, Zaikin, Alexey
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2891702/
https://www.ncbi.nlm.nih.gov/pubmed/20613855
http://dx.doi.org/10.1371/journal.pcbi.1000830
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author Liepe, Juliane
Mishto, Michele
Textoris-Taube, Kathrin
Janek, Katharina
Keller, Christin
Henklein, Petra
Kloetzel, Peter Michael
Zaikin, Alexey
author_facet Liepe, Juliane
Mishto, Michele
Textoris-Taube, Kathrin
Janek, Katharina
Keller, Christin
Henklein, Petra
Kloetzel, Peter Michael
Zaikin, Alexey
author_sort Liepe, Juliane
collection PubMed
description The identification of proteasome-generated spliced peptides (PSP) revealed a new unpredicted activity of the major cellular protease. However, so far characterization of PSP was entirely dependent on the availability of patient-derived cytotoxic CD8+ T lymphocytes (CTL) thus preventing a systematic investigation of proteasome-catalyzed peptide splicing (PCPS). For an unrestricted PSP identification we here developed SpliceMet, combining the computer-based algorithm ProteaJ with in vitro proteasomal degradation assays and mass spectrometry. By applying SpliceMet for the analysis of proteasomal processing products of four different substrate polypeptides, derived from human tumor as well as viral antigens, we identified fifteen new spliced peptides generated by PCPS either by cis or from two separate substrate molecules, i.e., by trans splicing. Our data suggest that 20S proteasomes represent a molecular machine that, due to its catalytic and structural properties, facilitates the generation of spliced peptides, thereby providing a pool of qualitatively new peptides from which functionally relevant products may be selected.
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spelling pubmed-28917022010-07-07 The 20S Proteasome Splicing Activity Discovered by SpliceMet Liepe, Juliane Mishto, Michele Textoris-Taube, Kathrin Janek, Katharina Keller, Christin Henklein, Petra Kloetzel, Peter Michael Zaikin, Alexey PLoS Comput Biol Research Article The identification of proteasome-generated spliced peptides (PSP) revealed a new unpredicted activity of the major cellular protease. However, so far characterization of PSP was entirely dependent on the availability of patient-derived cytotoxic CD8+ T lymphocytes (CTL) thus preventing a systematic investigation of proteasome-catalyzed peptide splicing (PCPS). For an unrestricted PSP identification we here developed SpliceMet, combining the computer-based algorithm ProteaJ with in vitro proteasomal degradation assays and mass spectrometry. By applying SpliceMet for the analysis of proteasomal processing products of four different substrate polypeptides, derived from human tumor as well as viral antigens, we identified fifteen new spliced peptides generated by PCPS either by cis or from two separate substrate molecules, i.e., by trans splicing. Our data suggest that 20S proteasomes represent a molecular machine that, due to its catalytic and structural properties, facilitates the generation of spliced peptides, thereby providing a pool of qualitatively new peptides from which functionally relevant products may be selected. Public Library of Science 2010-06-24 /pmc/articles/PMC2891702/ /pubmed/20613855 http://dx.doi.org/10.1371/journal.pcbi.1000830 Text en Liepe et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Liepe, Juliane
Mishto, Michele
Textoris-Taube, Kathrin
Janek, Katharina
Keller, Christin
Henklein, Petra
Kloetzel, Peter Michael
Zaikin, Alexey
The 20S Proteasome Splicing Activity Discovered by SpliceMet
title The 20S Proteasome Splicing Activity Discovered by SpliceMet
title_full The 20S Proteasome Splicing Activity Discovered by SpliceMet
title_fullStr The 20S Proteasome Splicing Activity Discovered by SpliceMet
title_full_unstemmed The 20S Proteasome Splicing Activity Discovered by SpliceMet
title_short The 20S Proteasome Splicing Activity Discovered by SpliceMet
title_sort 20s proteasome splicing activity discovered by splicemet
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2891702/
https://www.ncbi.nlm.nih.gov/pubmed/20613855
http://dx.doi.org/10.1371/journal.pcbi.1000830
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