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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
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.
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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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