Constitutive Activation of p62/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell Lymphoma

Detalhes bibliográficos
Autor(a) principal: Quinet, Grégoire
Data de Publicação: 2022
Outros Autores: 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.
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.
id RCAP_4bcf231edf876b0a56bc1001c1fbfe3e
oai_identifier_str oai:run.unl.pt:10362/134490
network_acronym_str RCAP
network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository_id_str 7160
spelling 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
instname_str 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
repository.mail.fl_str_mv
_version_ 1799138082438512640

Registros relacionados