Constitutive Activation of p62/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell Lymphoma
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10362/134490 |
Resumo: | Funding Information: Funding: This work was supported at early stages by Spanish MINECO, CTQ2011–27874 grant. M.G.-S. is a fellow of the UbiCODE project funded by the EU’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 765445. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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7160 |
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Constitutive Activation of p62/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell LymphomaApoptosisAutophagyProteasome inhibitorTUBEsUbiquitin proteomeVerteporfinOncologyCancer ResearchSDG 3 - Good Health and Well-beingFunding Information: Funding: This work was supported at early stages by Spanish MINECO, CTQ2011–27874 grant. M.G.-S. is a fellow of the UbiCODE project funded by the EU’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 765445.Protein ubiquitylation coordinates crucial cellular events in physiological and pathological conditions. A comparative analysis of the ubiquitin proteome from bortezomib (BTZ)-sensitive and BTZ-resistant mantle cell lymphoma (MCL) revealed an enrichment of the autophagy-lysosome system (ALS) in BTZ-resistant cells. Pharmacological inhibition of autophagy at the level of lysosome-fusion revealed a constitutive activation of proteaphagy and accumulation of proteasome subunits within autophagosomes in different MCL cell lines with acquired or natural resistance to BTZ. Inhibition of the autophagy receptor p62/SQSTM1 upon verteporfin (VTP) treatment disrupted proteaphagosome assembly, reduced co-localization of proteasome subunits with autophagy markers and negatively impacted proteasome activity. Finally, the silencing or pharmacological inhibition of p62 restored the apoptosis threshold at physiological levels in BTZ-resistant cells both in vitro and in vivo. In total, these results demonstrate for the first time a proteolytic switch from the ubiquitin-proteasome system (UPS) to ALS in B-cell lymphoma refractory to proteasome inhibition, pointing out a crucial role for proteaphagy in this phenomenon and paving the way for the design of alternative therapeutic venues in treatment-resistant tumors.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)RUNQuinet, GrégoireXolalpa, WendyReyes-Garau, DianaProfitós-Pelejà, NúriaAzkargorta, MikelCeccato, LaurieGonzalez-Santamarta, MariaMarsal, MariaAndilla, JordiAillet, FabienneBosch, FrancescElortza, FelixLoza-Alvarez, PabloSola, BrigitteCoux, OlivierMatthiesen, RuneRoué, GaëlRodriguez, Manuel S.2022-03-14T23:23:02Z2022-02-012022-02-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/134490eng2072-6694PURE: 42051362https://doi.org/10.3390/cancers14040923info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:12:53Zoai:run.unl.pt:10362/134490Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:48:05.796703Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Constitutive Activation of p62/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell Lymphoma |
title |
Constitutive Activation of p62/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell Lymphoma |
spellingShingle |
Constitutive Activation of p62/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell Lymphoma Quinet, Grégoire Apoptosis Autophagy Proteasome inhibitor TUBEs Ubiquitin proteome Verteporfin Oncology Cancer Research SDG 3 - Good Health and Well-being |
title_short |
Constitutive Activation of p62/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell Lymphoma |
title_full |
Constitutive Activation of p62/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell Lymphoma |
title_fullStr |
Constitutive Activation of p62/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell Lymphoma |
title_full_unstemmed |
Constitutive Activation of p62/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell Lymphoma |
title_sort |
Constitutive Activation of p62/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell Lymphoma |
author |
Quinet, Grégoire |
author_facet |
Quinet, Grégoire Xolalpa, Wendy Reyes-Garau, Diana Profitós-Pelejà, Núria Azkargorta, Mikel Ceccato, Laurie Gonzalez-Santamarta, Maria Marsal, Maria Andilla, Jordi Aillet, Fabienne Bosch, Francesc Elortza, Felix Loza-Alvarez, Pablo Sola, Brigitte Coux, Olivier Matthiesen, Rune Roué, Gaël Rodriguez, Manuel S. |
author_role |
author |
author2 |
Xolalpa, Wendy Reyes-Garau, Diana Profitós-Pelejà, Núria Azkargorta, Mikel Ceccato, Laurie Gonzalez-Santamarta, Maria Marsal, Maria Andilla, Jordi Aillet, Fabienne Bosch, Francesc Elortza, Felix Loza-Alvarez, Pablo Sola, Brigitte Coux, Olivier Matthiesen, Rune Roué, Gaël Rodriguez, Manuel S. |
author2_role |
author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) Centro de Estudos de Doenças Crónicas (CEDOC) RUN |
dc.contributor.author.fl_str_mv |
Quinet, Grégoire Xolalpa, Wendy Reyes-Garau, Diana Profitós-Pelejà, Núria Azkargorta, Mikel Ceccato, Laurie Gonzalez-Santamarta, Maria Marsal, Maria Andilla, Jordi Aillet, Fabienne Bosch, Francesc Elortza, Felix Loza-Alvarez, Pablo Sola, Brigitte Coux, Olivier Matthiesen, Rune Roué, Gaël Rodriguez, Manuel S. |
dc.subject.por.fl_str_mv |
Apoptosis Autophagy Proteasome inhibitor TUBEs Ubiquitin proteome Verteporfin Oncology Cancer Research SDG 3 - Good Health and Well-being |
topic |
Apoptosis Autophagy Proteasome inhibitor TUBEs Ubiquitin proteome Verteporfin Oncology Cancer Research SDG 3 - Good Health and Well-being |
description |
Funding Information: Funding: This work was supported at early stages by Spanish MINECO, CTQ2011–27874 grant. M.G.-S. is a fellow of the UbiCODE project funded by the EU’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 765445. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-03-14T23:23:02Z 2022-02-01 2022-02-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/134490 |
url |
http://hdl.handle.net/10362/134490 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2072-6694 PURE: 42051362 https://doi.org/10.3390/cancers14040923 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799138082438512640 |