Decrypting drug actions and protein modifications by dose- and time-resolved proteomics.
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
07 04 2023
07 04 2023
Historique:
medline:
10
4
2023
pubmed:
18
3
2023
entrez:
17
3
2023
Statut:
ppublish
Résumé
Although most cancer drugs modulate the activities of cellular pathways by changing posttranslational modifications (PTMs), little is known regarding the extent and the time- and dose-response characteristics of drug-regulated PTMs. In this work, we introduce a proteomic assay called decryptM that quantifies drug-PTM modulation for thousands of PTMs in cells to shed light on target engagement and drug mechanism of action. Examples range from detecting DNA damage by chemotherapeutics, to identifying drug-specific PTM signatures of kinase inhibitors, to demonstrating that rituximab kills CD20-positive B cells by overactivating B cell receptor signaling. DecryptM profiling of 31 cancer drugs in 13 cell lines demonstrates the broad applicability of the approach. The resulting 1.8 million dose-response curves are provided as an interactive molecular resource in ProteomicsDB.
Identifiants
pubmed: 36926954
doi: 10.1126/science.ade3925
pmc: PMC7615311
mid: EMS173913
doi:
Substances chimiques
Antigens, CD20
0
Antineoplastic Agents
0
Receptors, Antigen, B-Cell
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
93-101Subventions
Organisme : European Research Council
ID : 833710
Pays : International
Commentaires et corrections
Type : CommentIn
Références
Mol Cell Proteomics. 2022 Apr;21(4):100221
pubmed: 35227894
J Med Chem. 2010 Apr 8;53(7):2719-40
pubmed: 20131845
Front Genet. 2019 Jun 04;10:514
pubmed: 31214247
Immunity. 2006 Nov;25(5):701-15
pubmed: 17098202
Nat Biotechnol. 2020 Mar;38(3):365-373
pubmed: 31819260
Sci Rep. 2019 Jul 19;9(1):10503
pubmed: 31324866
ACS Chem Biol. 2019 Apr 19;14(4):655-664
pubmed: 30901187
J Exp Med. 1997 Dec 1;186(11):1897-910
pubmed: 9382888
Mol Cell Proteomics. 2019 Jul;18(7):1468-1478
pubmed: 30967486
PLoS One. 2018 Jan 23;13(1):e0191634
pubmed: 29360859
Nucleic Acids Res. 2022 Jan 7;50(D1):D1541-D1552
pubmed: 34791421
Nucleic Acids Res. 2015 Jan;43(Database issue):D512-20
pubmed: 25514926
Science. 2023 Apr 7;380(6640):93-101
pubmed: 36926954
Curr Opin Chem Biol. 2021 Feb;60:20-29
pubmed: 32768892
Nucleic Acids Res. 2011 Jan;39(Database issue):D261-7
pubmed: 21062810
Mol Cell Biol. 2003 Aug;23(16):5790-802
pubmed: 12897149
J Cancer. 2017 Sep 12;8(16):3131-3141
pubmed: 29158785
Nat Immunol. 2006 Jun;7(6):625-33
pubmed: 16648854
EMBO Rep. 2016 Oct;17(10):1374-1395
pubmed: 27629041
Mol Cell Proteomics. 2015 Jan;14(1):205-15
pubmed: 25394399
Methods Mol Biol. 2017;1550:83-98
pubmed: 28188525
Nucleic Acids Res. 2019 Jul 2;47(W1):W191-W198
pubmed: 31066453
Nature. 2016 Jul 7;535(7610):148-52
pubmed: 27362227
Nat Biotechnol. 2008 Dec;26(12):1367-72
pubmed: 19029910
Front Oncol. 2018 Jun 04;8:163
pubmed: 29915719
Nat Commun. 2020 Jan 9;11(1):157
pubmed: 31919466
Genome Res. 2003 Nov;13(11):2498-504
pubmed: 14597658
Cell. 2018 Jun 28;174(1):231-244.e12
pubmed: 29804834
Nat Methods. 2011 Oct 02;8(11):937-40
pubmed: 21963607
Front Immunol. 2020 Nov 19;11:584509
pubmed: 33329558
Redox Biol. 2021 Nov;47:102170
pubmed: 34688156
Science. 2014 Oct 3;346(6205):1255784
pubmed: 25278616
Arch Biochem Biophys. 2018 Feb 1;639:52-58
pubmed: 29305052
Nucleic Acids Res. 2019 Jan 8;47(D1):D442-D450
pubmed: 30395289
N Engl J Med. 2007 Jul 5;357(1):39-51
pubmed: 17611206
Cell Death Dis. 2017 Aug 31;8(8):e3026
pubmed: 29048431
EMBO J. 2003 Jun 16;22(12):3015-26
pubmed: 12805216
Nature. 2017 Oct 5;550(7674):128-132
pubmed: 28953875
Cancer Cell. 2015 Jul 13;28(1):114-28
pubmed: 26073130
Cancer Res. 2010 Jan 15;70(2):440-6
pubmed: 20068163
PLoS One. 2015 Dec 30;10(12):e0146021
pubmed: 26717316
Immunity. 1997 Apr;6(4):419-28
pubmed: 9133421
iScience. 2021 Jan 22;24(2):102089
pubmed: 33615197
Cancers (Basel). 2018 Sep 20;10(10):
pubmed: 30241301
Nat Chem Biol. 2022 Aug;18(8):812-820
pubmed: 35484434
Expert Rev Proteomics. 2021 Jul;18(7):503-526
pubmed: 34320887
Nat Biotechnol. 2015 Apr;33(4):415-23
pubmed: 25751058
Nucleic Acids Res. 2021 Jan 8;49(D1):D480-D489
pubmed: 33237286
Nat Commun. 2015 Dec 03;6:10091
pubmed: 26631872
Sci Rep. 2015 Nov 30;5:17409
pubmed: 26616534
Mol Cell. 2007 Jul 20;27(2):197-213
pubmed: 17643370
Science. 2017 Dec 1;358(6367):
pubmed: 29191878
Nat Protoc. 2019 Jan;14(1):68-85
pubmed: 30464214
Anal Chem. 2003 Apr 15;75(8):1895-904
pubmed: 12713048
Front Immunol. 2021 Aug 09;12:716469
pubmed: 34434197
Drug Metab Pharmacokinet. 2015 Oct;30(5):366-73
pubmed: 26427316
EMBO J. 2010 Mar 3;29(5):969-80
pubmed: 20075865
Cancer Treat Rev. 2021 Jan;92:102137
pubmed: 33340965
Nat Commun. 2021 Jan 4;12(1):62
pubmed: 33397936
Cell Prolif. 2007 Aug;40(4):488-507
pubmed: 17635517