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Starvation-induced proteasome assemblies in the nucleus link amino acid supply to apoptosis
Eukaryotic cells have evolved highly orchestrated protein catabolic machineries responsible for the timely and selective disposal of proteins and organelles, thereby ensuring amino acid recycling. However, how protein degradation is coordinated with amino acid supply and protein synthesis has remain...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8633328/ https://www.ncbi.nlm.nih.gov/pubmed/34848715 http://dx.doi.org/10.1038/s41467-021-27306-4 |
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author | Uriarte, Maxime Sen Nkwe, Nadine Tremblay, Roch Ahmed, Oumaima Messmer, Clémence Mashtalir, Nazar Barbour, Haithem Masclef, Louis Voide, Marion Viallard, Claire Daou, Salima Abdelhadi, Djaileb Ronato, Daryl Paydar, Mohammadjavad Darracq, Anaïs Boulay, Karine Desjardins-Lecavalier, Nicolas Sapieha, Przemyslaw Masson, Jean-Yves Sergeev, Mikhail Kwok, Benjamin H. Hulea, Laura Mallette, Frédérick A. Milot, Eric Larrivée, Bruno Wurtele, Hugo Affar, El Bachir |
author_facet | Uriarte, Maxime Sen Nkwe, Nadine Tremblay, Roch Ahmed, Oumaima Messmer, Clémence Mashtalir, Nazar Barbour, Haithem Masclef, Louis Voide, Marion Viallard, Claire Daou, Salima Abdelhadi, Djaileb Ronato, Daryl Paydar, Mohammadjavad Darracq, Anaïs Boulay, Karine Desjardins-Lecavalier, Nicolas Sapieha, Przemyslaw Masson, Jean-Yves Sergeev, Mikhail Kwok, Benjamin H. Hulea, Laura Mallette, Frédérick A. Milot, Eric Larrivée, Bruno Wurtele, Hugo Affar, El Bachir |
author_sort | Uriarte, Maxime |
collection | PubMed |
description | Eukaryotic cells have evolved highly orchestrated protein catabolic machineries responsible for the timely and selective disposal of proteins and organelles, thereby ensuring amino acid recycling. However, how protein degradation is coordinated with amino acid supply and protein synthesis has remained largely elusive. Here we show that the mammalian proteasome undergoes liquid-liquid phase separation in the nucleus upon amino acid deprivation. We termed these proteasome condensates SIPAN (Starvation-Induced Proteasome Assemblies in the Nucleus) and show that these are a common response of mammalian cells to amino acid deprivation. SIPAN undergo fusion events, rapidly exchange proteasome particles with the surrounding milieu and quickly dissolve following amino acid replenishment. We further show that: (i) SIPAN contain K48-conjugated ubiquitin, (ii) proteasome inhibition accelerates SIPAN formation, (iii) deubiquitinase inhibition prevents SIPAN resolution and (iv) RAD23B proteasome shuttling factor is required for SIPAN formation. Finally, SIPAN formation is associated with decreased cell survival and p53-mediated apoptosis, which might contribute to tissue fitness in diverse pathophysiological conditions. |
format | Online Article Text |
id | pubmed-8633328 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-86333282021-12-15 Starvation-induced proteasome assemblies in the nucleus link amino acid supply to apoptosis Uriarte, Maxime Sen Nkwe, Nadine Tremblay, Roch Ahmed, Oumaima Messmer, Clémence Mashtalir, Nazar Barbour, Haithem Masclef, Louis Voide, Marion Viallard, Claire Daou, Salima Abdelhadi, Djaileb Ronato, Daryl Paydar, Mohammadjavad Darracq, Anaïs Boulay, Karine Desjardins-Lecavalier, Nicolas Sapieha, Przemyslaw Masson, Jean-Yves Sergeev, Mikhail Kwok, Benjamin H. Hulea, Laura Mallette, Frédérick A. Milot, Eric Larrivée, Bruno Wurtele, Hugo Affar, El Bachir Nat Commun Article Eukaryotic cells have evolved highly orchestrated protein catabolic machineries responsible for the timely and selective disposal of proteins and organelles, thereby ensuring amino acid recycling. However, how protein degradation is coordinated with amino acid supply and protein synthesis has remained largely elusive. Here we show that the mammalian proteasome undergoes liquid-liquid phase separation in the nucleus upon amino acid deprivation. We termed these proteasome condensates SIPAN (Starvation-Induced Proteasome Assemblies in the Nucleus) and show that these are a common response of mammalian cells to amino acid deprivation. SIPAN undergo fusion events, rapidly exchange proteasome particles with the surrounding milieu and quickly dissolve following amino acid replenishment. We further show that: (i) SIPAN contain K48-conjugated ubiquitin, (ii) proteasome inhibition accelerates SIPAN formation, (iii) deubiquitinase inhibition prevents SIPAN resolution and (iv) RAD23B proteasome shuttling factor is required for SIPAN formation. Finally, SIPAN formation is associated with decreased cell survival and p53-mediated apoptosis, which might contribute to tissue fitness in diverse pathophysiological conditions. Nature Publishing Group UK 2021-11-30 /pmc/articles/PMC8633328/ /pubmed/34848715 http://dx.doi.org/10.1038/s41467-021-27306-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Uriarte, Maxime Sen Nkwe, Nadine Tremblay, Roch Ahmed, Oumaima Messmer, Clémence Mashtalir, Nazar Barbour, Haithem Masclef, Louis Voide, Marion Viallard, Claire Daou, Salima Abdelhadi, Djaileb Ronato, Daryl Paydar, Mohammadjavad Darracq, Anaïs Boulay, Karine Desjardins-Lecavalier, Nicolas Sapieha, Przemyslaw Masson, Jean-Yves Sergeev, Mikhail Kwok, Benjamin H. Hulea, Laura Mallette, Frédérick A. Milot, Eric Larrivée, Bruno Wurtele, Hugo Affar, El Bachir Starvation-induced proteasome assemblies in the nucleus link amino acid supply to apoptosis |
title | Starvation-induced proteasome assemblies in the nucleus link amino acid supply to apoptosis |
title_full | Starvation-induced proteasome assemblies in the nucleus link amino acid supply to apoptosis |
title_fullStr | Starvation-induced proteasome assemblies in the nucleus link amino acid supply to apoptosis |
title_full_unstemmed | Starvation-induced proteasome assemblies in the nucleus link amino acid supply to apoptosis |
title_short | Starvation-induced proteasome assemblies in the nucleus link amino acid supply to apoptosis |
title_sort | starvation-induced proteasome assemblies in the nucleus link amino acid supply to apoptosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8633328/ https://www.ncbi.nlm.nih.gov/pubmed/34848715 http://dx.doi.org/10.1038/s41467-021-27306-4 |
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