Imaging-Based Screening of Deubiquitinating Proteases Identifies Otubain-1 as a Stabilizer of c-MYC.
OTUB1
c-MYC
deubiquitinase
deubiquitinating protease
genetic screen
high-content imaging
oncogene
protein degradation
protein turnover
ubiquitin–proteasome system
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
04 Feb 2022
04 Feb 2022
Historique:
received:
23
12
2021
revised:
01
02
2022
accepted:
02
02
2022
entrez:
15
2
2022
pubmed:
16
2
2022
medline:
16
2
2022
Statut:
epublish
Résumé
The ubiquitin-proteasome pathway precisely controls the turnover of transcription factors in the nucleus, playing an important role in maintaining appropriate quantities of these regulatory proteins. The transcription factor c-MYC is essential for normal development and is a critical cancer driver. Despite being highly expressed in several tissues and malignancies, the c-MYC protein is also continuously targeted by the ubiquitin-proteasome pathway, which can either facilitate or inhibit c-MYC degradation. Deubiquitinating proteases can remove ubiquitin chains from target proteins and rescue them from proteasomal digestion. This study sought to determine novel elements of the ubiquitin-proteasome pathway that regulate c-MYC levels. We performed an overexpression screen with 41 human proteases to identify which deubiquitinases stabilize c-MYC. We discovered that the highly expressed Otubain-1 (OTUB1) protease increases c-MYC protein levels. Confirming its role in enhancing c-MYC activity, we found that elevated OTUB1 correlates with inferior clinical outcomes in the c-MYC-dependent cancer multiple myeloma, and overexpression of OTUB1 accelerates the growth of myeloma cells. In summary, our study identifies OTUB1 as a novel amplifier of the proto-oncogene c-MYC.
Identifiants
pubmed: 35159073
pii: cancers14030806
doi: 10.3390/cancers14030806
pmc: PMC8833929
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : NIH HHS
ID : T32DK60445, R01DK115454, R01GM142143
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK115454
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK060445
Pays : United States
Organisme : CPRIT
ID : RR140038
Organisme : NIGMS NIH HHS
ID : R01 GM142143
Pays : United States
Références
FEBS Lett. 2016 Apr;590(7):908-23
pubmed: 26832397
N Engl J Med. 2005 Jun 16;352(24):2487-98
pubmed: 15958804
Annu Rev Biochem. 2012;81:177-201
pubmed: 22404630
Nat Rev Cancer. 2015 Oct;15(10):593-607
pubmed: 26383138
Mol Endocrinol. 2009 May;23(5):587-9
pubmed: 19221049
Front Oncol. 2021 Jun 11;11:679445
pubmed: 34178666
Cancer Res. 2018 May 15;78(10):2449-2456
pubmed: 29703720
Blood. 2021 Mar 18;137(11):1478-1490
pubmed: 32842143
Cell. 2005 Nov 4;123(3):409-21
pubmed: 16269333
Curr Biol. 2004 Oct 26;14(20):1852-7
pubmed: 15498494
Sci Signal. 2015 Apr 14;8(372):ra35
pubmed: 25872870
Nature. 2018 Nov;563(7731):407-411
pubmed: 30429547
Trends Cell Biol. 2015 Jul;25(7):417-26
pubmed: 25906909
Chembiochem. 2005 Feb;6(2):287-91
pubmed: 15651044
Cell. 2013 Dec 5;155(6):1380-95
pubmed: 24315104
Curr Top Microbiol Immunol. 2006;302:1-32
pubmed: 16620023
Nat Rev Drug Discov. 2018 Jan;17(1):57-78
pubmed: 28959952
Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3118-23
pubmed: 10706616
PLoS One. 2008 Jan 23;3(1):e1487
pubmed: 18213395
Sci Signal. 2019 Jul 16;12(590):
pubmed: 31311847
PLoS One. 2015 Jan 15;10(1):e0115344
pubmed: 25590432
Adv Cancer Res. 2008;99:113-333
pubmed: 18037408
Cancer Discov. 2015 Oct;5(10):1024-39
pubmed: 26382145
Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):9085-90
pubmed: 15150404
Cold Spring Harb Perspect Med. 2013 Nov 01;3(11):
pubmed: 24186489
Adv Cancer Res. 2011;110:77-106
pubmed: 21704229
Nat Genet. 2012 Dec;44(12):1321-5
pubmed: 23143597
Genes Dev. 2008 Oct 15;22(20):2755-66
pubmed: 18923074
Chem Biol. 2002 Oct;9(10):1149-59
pubmed: 12401499
Nat Struct Mol Biol. 2013 Sep;20(9):1033-9
pubmed: 23955022
Cell Biosci. 2016 Dec 20;6:62
pubmed: 28031783
Cell Cycle. 2009 Jun 1;8(11):1688-97
pubmed: 19448430
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
Int J Biochem Cell Biol. 2012 Nov;44(11):1729-38
pubmed: 22819849
J Clin Invest. 2014 Aug;124(8):3407-18
pubmed: 24960159
Nat Chem Biol. 2007 Nov;3(11):697-705
pubmed: 17948018
PLoS One. 2011;6(11):e27988
pubmed: 22132187
Annu Rev Biochem. 2017 Jun 20;86:159-192
pubmed: 28498721
EMBO J. 2004 May 19;23(10):2116-25
pubmed: 15103331
J Exp Med. 2017 Jan;214(1):245-267
pubmed: 27923907
Per Med. 2012 May;9(3):333-336
pubmed: 29758781
Cell. 1994 Sep 9;78(5):761-71
pubmed: 8087844
Cancer Discov. 2012 Mar;2(3):206-7
pubmed: 22585990
Trends Cell Biol. 2015 Apr;25(4):241-8
pubmed: 25475704
Cell. 2012 Mar 30;149(1):22-35
pubmed: 22464321
Cell. 2015 Jan 29;160(3):477-88
pubmed: 25619689
Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):228-33
pubmed: 10618400
Sci Rep. 2020 Aug 18;10(1):13942
pubmed: 32811853
Endocr Relat Cancer. 2019 Jan 1;26(1):R1-R14
pubmed: 30400005
Cold Spring Harb Perspect Med. 2014 Mar 01;4(3):
pubmed: 24591536
Mol Cell. 2012 Feb 10;45(3):384-97
pubmed: 22325355
Nat Cell Biol. 2003 Oct;5(10):845-50
pubmed: 14523392
J Biol Chem. 2018 Nov 23;293(47):18285-18295
pubmed: 30282802
Mol Cell Biol. 1999 Jan;19(1):1-11
pubmed: 9858526
Cell Oncol (Dordr). 2015 Aug;38(4):265-77
pubmed: 25925205
Front Mol Biosci. 2020 Feb 27;7:21
pubmed: 32175328
Int J Biochem Cell Biol. 2021 Aug;137:106023
pubmed: 34102342
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
Proc Natl Acad Sci U S A. 2015 Mar 24;112(12):3734-9
pubmed: 25775507
Ageing Res Rev. 2021 May;67:101303
pubmed: 33609777
Nat Cell Biol. 2007 Jul;9(7):765-74
pubmed: 17558397
Cancers (Basel). 2021 Feb 17;13(4):
pubmed: 33671345
Genes Dis. 2019 Jul 24;6(4):359-371
pubmed: 31832515
Eur J Immunol. 2008 Feb;38(2):342-9
pubmed: 18196519
J Biomed Sci. 2019 May 27;26(1):42
pubmed: 31133011
Nat Cell Biol. 2010 Oct;12(10):973-81
pubmed: 20852628
EMBO J. 1999 Feb 1;18(3):717-26
pubmed: 9927431
Cancer Metastasis Rev. 2017 Dec;36(4):669-682
pubmed: 29080080
J Microsc. 1993 Mar;169(3):375-382
pubmed: 33930978