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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...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2010
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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. |
format | Text |
id | pubmed-2891702 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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