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Quantitative measurement of the requirement of diverse protein degradation pathways in MHC class I peptide presentation
Peptides from degradation of intracellular proteins are continuously displayed by major histocompatibility complex (MHC) class I. To better understand origins of these peptides, we performed a comprehensive census of the class I peptide repertoire in the presence and absence of ubiquitin-proteasome...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10289651/ https://www.ncbi.nlm.nih.gov/pubmed/37352349 http://dx.doi.org/10.1126/sciadv.ade7890 |
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author | Mamrosh, Jennifer L. Sherman, David J. Cohen, Joseph R. Johnston, James A. Joubert, Marisa K. Li, Jing Lipford, J. Russell Lomenick, Brett Moradian, Annie Prabhu, Siddharth Sweredoski, Michael J. Vander Lugt, Bryan Verma, Rati Deshaies, Raymond J. |
author_facet | Mamrosh, Jennifer L. Sherman, David J. Cohen, Joseph R. Johnston, James A. Joubert, Marisa K. Li, Jing Lipford, J. Russell Lomenick, Brett Moradian, Annie Prabhu, Siddharth Sweredoski, Michael J. Vander Lugt, Bryan Verma, Rati Deshaies, Raymond J. |
author_sort | Mamrosh, Jennifer L. |
collection | PubMed |
description | Peptides from degradation of intracellular proteins are continuously displayed by major histocompatibility complex (MHC) class I. To better understand origins of these peptides, we performed a comprehensive census of the class I peptide repertoire in the presence and absence of ubiquitin-proteasome system (UPS) activity upon developing optimized methodology to enrich for and quantify these peptides. Whereas most class I peptides are dependent on the UPS for their generation, a surprising 30%, enriched in peptides of mitochondrial origin, appears independent of the UPS. A further ~10% of peptides were found to be dependent on the proteasome but independent of ubiquitination for their generation. Notably, clinically achievable partial inhibition of the proteasome resulted in display of atypical peptides. Our results suggest that generation of MHC class I•peptide complexes is more complex than previously recognized, with UPS-dependent and UPS-independent components; paradoxically, alternative protein degradation pathways also generate class I peptides when canonical pathways are impaired. |
format | Online Article Text |
id | pubmed-10289651 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-102896512023-06-24 Quantitative measurement of the requirement of diverse protein degradation pathways in MHC class I peptide presentation Mamrosh, Jennifer L. Sherman, David J. Cohen, Joseph R. Johnston, James A. Joubert, Marisa K. Li, Jing Lipford, J. Russell Lomenick, Brett Moradian, Annie Prabhu, Siddharth Sweredoski, Michael J. Vander Lugt, Bryan Verma, Rati Deshaies, Raymond J. Sci Adv Biomedicine and Life Sciences Peptides from degradation of intracellular proteins are continuously displayed by major histocompatibility complex (MHC) class I. To better understand origins of these peptides, we performed a comprehensive census of the class I peptide repertoire in the presence and absence of ubiquitin-proteasome system (UPS) activity upon developing optimized methodology to enrich for and quantify these peptides. Whereas most class I peptides are dependent on the UPS for their generation, a surprising 30%, enriched in peptides of mitochondrial origin, appears independent of the UPS. A further ~10% of peptides were found to be dependent on the proteasome but independent of ubiquitination for their generation. Notably, clinically achievable partial inhibition of the proteasome resulted in display of atypical peptides. Our results suggest that generation of MHC class I•peptide complexes is more complex than previously recognized, with UPS-dependent and UPS-independent components; paradoxically, alternative protein degradation pathways also generate class I peptides when canonical pathways are impaired. American Association for the Advancement of Science 2023-06-23 /pmc/articles/PMC10289651/ /pubmed/37352349 http://dx.doi.org/10.1126/sciadv.ade7890 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Mamrosh, Jennifer L. Sherman, David J. Cohen, Joseph R. Johnston, James A. Joubert, Marisa K. Li, Jing Lipford, J. Russell Lomenick, Brett Moradian, Annie Prabhu, Siddharth Sweredoski, Michael J. Vander Lugt, Bryan Verma, Rati Deshaies, Raymond J. Quantitative measurement of the requirement of diverse protein degradation pathways in MHC class I peptide presentation |
title | Quantitative measurement of the requirement of diverse protein degradation pathways in MHC class I peptide presentation |
title_full | Quantitative measurement of the requirement of diverse protein degradation pathways in MHC class I peptide presentation |
title_fullStr | Quantitative measurement of the requirement of diverse protein degradation pathways in MHC class I peptide presentation |
title_full_unstemmed | Quantitative measurement of the requirement of diverse protein degradation pathways in MHC class I peptide presentation |
title_short | Quantitative measurement of the requirement of diverse protein degradation pathways in MHC class I peptide presentation |
title_sort | quantitative measurement of the requirement of diverse protein degradation pathways in mhc class i peptide presentation |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10289651/ https://www.ncbi.nlm.nih.gov/pubmed/37352349 http://dx.doi.org/10.1126/sciadv.ade7890 |
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