Constitutive Activation of p62/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell Lymphoma.
TUBEs
apoptosis
autophagy
proteasome inhibitor
ubiquitin proteome
verteporfin
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
12 Feb 2022
12 Feb 2022
Historique:
received:
11
12
2021
revised:
01
02
2022
accepted:
07
02
2022
entrez:
25
2
2022
pubmed:
26
2
2022
medline:
26
2
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35205670
pii: cancers14040923
doi: 10.3390/cancers14040923
pmc: PMC8869867
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : European Union
ID : Grant agreement No 765445.
Organisme : French National Cancer Institute
ID : PLBIO16-251
Organisme : Consejo Nacional de Ciencia y Tecnología
ID : CONACYT-SRE 0280365
Organisme : Ministry of Economy, Industry and Competitiveness
ID : SEV-2015-0522
Organisme : LASERLAB Europe
ID : 654148
Organisme : Instituto de Salud Carlos III
ID : PI15/00102 and PI18/01383
Références
Elife. 2015 Sep 01;4:e08153
pubmed: 26327694
Methods Mol Biol. 2016;1449:177-92
pubmed: 27613035
Molecules. 2020 May 18;25(10):
pubmed: 32443527
FEBS Open Bio. 2021 Jan;11(1):48-60
pubmed: 33410599
Blood. 2011 Jan 27;117(4):1270-9
pubmed: 21106982
Cancers (Basel). 2020 Jun 12;12(6):
pubmed: 32545704
EMBO Rep. 2009 Nov;10(11):1250-8
pubmed: 19798103
Trends Biochem Sci. 2019 Jul;44(7):599-615
pubmed: 30819414
Methods Enzymol. 2005;398:353-63
pubmed: 16275342
Proc Natl Acad Sci U S A. 2013 Nov 5;110(45):18250-5
pubmed: 24145436
Methods Mol Biol. 2012;832:173-83
pubmed: 22350885
Oncotarget. 2016 Oct 11;7(41):66360-66385
pubmed: 27626179
Cell Rep. 2016 Aug 9;16(6):1717-1732
pubmed: 27477278
Biomed Res Int. 2015;2015:172458
pubmed: 26579531
Nat Biotechnol. 2008 Dec;26(12):1367-72
pubmed: 19029910
Trends Biochem Sci. 2017 Nov;42(11):873-886
pubmed: 28947091
Hematol Oncol Clin North Am. 2019 Aug;33(4):613-626
pubmed: 31229158
Br J Haematol. 2018 Jun;181(5):703-706
pubmed: 28444739
Adv Exp Med Biol. 2020;1233:153-174
pubmed: 32274756
Methods Enzymol. 2005;398:364-78
pubmed: 16275343
Autophagy. 2015;11(7):1161-78
pubmed: 26043024
Mol Cell. 2015 Jun 18;58(6):1053-66
pubmed: 26004230
Adv Exp Med Biol. 2020;1233:55-100
pubmed: 32274753
Mol Cell Proteomics. 2014 Dec;13(12):3294-307
pubmed: 25128556
Oncogene. 2018 Apr;37(14):1830-1844
pubmed: 29353886
Sci Rep. 2017 Apr 21;7:46581
pubmed: 28429726
Methods Mol Biol. 2016;1449:161-75
pubmed: 27613034
Elife. 2015 Sep 01;4:
pubmed: 26327695
Ther Adv Hematol. 2016 Aug;7(4):196-208
pubmed: 27493710
Drug Resist Updat. 2015 Jan;18:18-35
pubmed: 25670156
Eur J Haematol. 2018 Mar 30;:
pubmed: 29603798
Clin Cancer Res. 2011 Aug 1;17(15):5101-12
pubmed: 21712452
PLoS One. 2014 Dec 10;9(12):e114964
pubmed: 25494214
Leukemia. 2019 Feb;33(2):447-456
pubmed: 30026573
Annu Rev Biochem. 2017 Jun 20;86:193-224
pubmed: 28460188
J Proteomics. 2012 Jun 6;75(10):2998-3014
pubmed: 22178446
Proteomics. 2010 Aug;10(16):3040-4
pubmed: 20641139
Leukemia. 2014 Oct;28(10):2049-59
pubmed: 24721791
Proc Natl Acad Sci U S A. 2016 Nov 22;113(47):E7490-E7499
pubmed: 27791183
Front Endocrinol (Lausanne). 2018 Jun 29;9:344
pubmed: 30008697
Cancer Cell Int. 2021 Jan 14;21(1):52
pubmed: 33446200
J Proteomics. 2016 Apr 29;139:45-59
pubmed: 26972027
Autophagy. 2017 Apr 3;13(4):759-760
pubmed: 28121483
Autophagy. 2018;14(8):1435-1455
pubmed: 29940786
J Proteomics. 2012 Jul 16;75(13):4176-83
pubmed: 22626983
Free Radic Biol Med. 2011 Oct 1;51(7):1355-64
pubmed: 21767633
Leuk Lymphoma. 2018 Jul;59(7):1726-1729
pubmed: 29164964
Hematol Oncol. 2019 Jun;37 Suppl 1:66-69
pubmed: 31187531
BMC Bioinformatics. 2011 Jan 26;12:35
pubmed: 21269502
J Biol Chem. 2011 Mar 4;286(9):7290-300
pubmed: 21193398
Autophagy. 2015;11(10):1927-8
pubmed: 26291247
Cell. 2017 May 18;169(5):792-806
pubmed: 28525752