{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T10:48:45Z","timestamp":1764240525402,"version":"build-2065373602"},"reference-count":56,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,12]],"date-time":"2022-02-12T00:00:00Z","timestamp":1644624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","award":["Grant agreement No 765445."],"award-info":[{"award-number":["Grant agreement No 765445."]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006364","name":"French National Cancer Institute","doi-asserted-by":"publisher","award":["PLBIO16-251"],"award-info":[{"award-number":["PLBIO16-251"]}],"id":[{"id":"10.13039\/501100006364","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["CONACYT-SRE 0280365"],"award-info":[{"award-number":["CONACYT-SRE 0280365"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministry of Economy, Industry and Competitiveness","doi-asserted-by":"publisher","award":["SEV-2015-0522"],"award-info":[{"award-number":["SEV-2015-0522"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015668","name":"LASERLAB Europe","doi-asserted-by":"publisher","award":["654148"],"award-info":[{"award-number":["654148"]}],"id":[{"id":"10.13039\/100015668","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI15\/00102 and PI18\/01383"],"award-info":[{"award-number":["PI15\/00102 and PI18\/01383"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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\u2013lysosome 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\u2013proteasome 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.<\/jats:p>","DOI":"10.3390\/cancers14040923","type":"journal-article","created":{"date-parts":[[2022,2,13]],"date-time":"2022-02-13T20:32:30Z","timestamp":1644784350000},"page":"923","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Constitutive Activation of p62\/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell Lymphoma"],"prefix":"10.3390","volume":"14","author":[{"given":"Gr\u00e9goire","family":"Quinet","sequence":"first","affiliation":[{"name":"Laboratoire de Chimie de Coordination (LCC) CNRS-UPR8241, UPS, 31400 Toulouse, France"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2227-7364","authenticated-orcid":false,"given":"Wendy","family":"Xolalpa","sequence":"additional","affiliation":[{"name":"Proteomics Unit, CIC bioGUNE, Parque Tecnol\u00f3gico de Bizkaia, 48160 Derio, Spain"}]},{"given":"Diana","family":"Reyes-Garau","sequence":"additional","affiliation":[{"name":"Lymphoma Translational Group, UBIRed, Josep Carreras Leukaemia Research Institute, 08916 Badalona, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8923-6025","authenticated-orcid":false,"given":"N\u00faria","family":"Profit\u00f3s-Pelej\u00e0","sequence":"additional","affiliation":[{"name":"Lymphoma Translational Group, UBIRed, Josep Carreras Leukaemia Research Institute, 08916 Badalona, Spain"}]},{"given":"Mikel","family":"Azkargorta","sequence":"additional","affiliation":[{"name":"Proteomics Platform CICbioGUNE, Basque Research and Technology Alliance (BRTA), CIBERehd, ProteoRed-ISCIII, Parque Tecnol\u00f3gico de Bizkaia, 31400 Derio, Spain"}]},{"given":"Laurie","family":"Ceccato","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie de Coordination (LCC) CNRS-UPR8241, UPS, 31400 Toulouse, France"}]},{"given":"Maria","family":"Gonzalez-Santamarta","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie de Coordination (LCC) CNRS-UPR8241, UPS, 31400 Toulouse, France"}]},{"given":"Maria","family":"Marsal","sequence":"additional","affiliation":[{"name":"ICFO-Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, 08860 Castelldefels, Spain"}]},{"given":"Jordi","family":"Andilla","sequence":"additional","affiliation":[{"name":"ICFO-Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, 08860 Castelldefels, Spain"}]},{"given":"Fabienne","family":"Aillet","sequence":"additional","affiliation":[{"name":"Proteomics Unit, CIC bioGUNE, Parque Tecnol\u00f3gico de Bizkaia, 48160 Derio, Spain"}]},{"given":"Francesc","family":"Bosch","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Hematology, Department of Hematology, Vall d\u2019Hebron Institute of Oncology, Vall d\u2019Hebron University Hospital, 08035 Barcelona, Spain"}]},{"given":"Felix","family":"Elortza","sequence":"additional","affiliation":[{"name":"Proteomics Platform CICbioGUNE, Basque Research and Technology Alliance (BRTA), CIBERehd, ProteoRed-ISCIII, Parque Tecnol\u00f3gico de Bizkaia, 31400 Derio, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3129-1213","authenticated-orcid":false,"given":"Pablo","family":"Loza-Alvarez","sequence":"additional","affiliation":[{"name":"ICFO-Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, 08860 Castelldefels, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7278-9651","authenticated-orcid":false,"given":"Brigitte","family":"Sola","sequence":"additional","affiliation":[{"name":"INSERM UMR1245, Unicaen, 14000 Caen, France"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8455-3849","authenticated-orcid":false,"given":"Olivier","family":"Coux","sequence":"additional","affiliation":[{"name":"Centre de Recherche de Biologie Cellulaire de Montpellier (CRBM) CNRS-UMR 5237, Universit\u00e9 de Montpellier, 34293 Montpellier, France"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6353-2616","authenticated-orcid":false,"given":"Rune","family":"Matthiesen","sequence":"additional","affiliation":[{"name":"Computational and Experimental Biology Group, CEDOC-Chronic Diseases Research Center, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade Nova de Lisboa, 1150-082 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0245-2257","authenticated-orcid":false,"given":"Ga\u00ebl","family":"Rou\u00e9","sequence":"additional","affiliation":[{"name":"Lymphoma Translational Group, UBIRed, Josep Carreras Leukaemia Research Institute, 08916 Badalona, Spain"}]},{"given":"Manuel 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