Constitutive Activation of p62/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell Lymphoma
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2022 |
| Outros Autores: | , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) |
| 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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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:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2024-05-22T18:00:09Zoai:run.unl.pt:10362/134490Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T17:31:03.205923Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse |
| 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 |
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info:eu-repo/semantics/article |
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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 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) |
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Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia |
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