Decrypting drug actions and protein modifications by dose- and time-resolved proteomics

被引：36

作者：

Zecha, Jana ^{[1
,2
]}

Bayer, Florian P. ^{[1
]}

Wiechmann, Svenja ^{[1
,2
]}

Woortman, Julia ^{[1
]}

Berner, Nicola ^{[1
,2
]}

Mueller, Julian ^{[1
]}

Schneider, Annika ^{[1
]}

Kramer, Karl ^{[1
]}

Abril-Gil, Mar ^{[3
]}

Hopf, Thomas ^{[4
]}

Reichart, Leonie ^{[4
]}

Chen, Lin ^{[1
]}

Hansen, Fynn M. ^{[1
,10
]}

Lechner, Severin ^{[1
]}

Samaras, Patroklos ^{[1
]}

Eckert, Stephan ^{[1
,2
]}

Lautenbacher, Ludwig ^{[1
]}

Reinecke, Maria ^{[1
]}

Hamood, Firas ^{[1
]}

Prokofeva, Polina ^{[1
]}

Vornholz, Larsen ^{[3
]}

Falcomata, Chiara ^{[2
,5
]}

Dorsch, Madeleine ^{[6
,7
]}

Schroeder, Ayla ^{[4
]}

Venhuizen, Anton ^{[1
]}

Wilhelm, Stephanie ^{[1
]}

Medard, Guillaume ^{[1
]}

Stoehr, Gabriele ^{[4
]}

Ruland, Juergen ^{[2
,3
,8
,9
]}

Gruener, Barbara M. ^{[6
,7
]}

Saur, Dieter ^{[2
,5
]}

Buchner, Maike ^{[3
]}

Ruprecht, Benjamin ^{[1
]}

Hahne, Hannes ^{[4
]}

The, Matthew ^{[1
]}

Wilhelm, Mathias ^{[1
]}

Kuster, Bernhard ^{[1
,2
]}

机构：

[1] Tech Univ Munich, Sch Life Sci, Dept Mol Life Sci, Prote & Bioanalyt, D-85354 Freising Weihenstephan, Germany

[2] German Canc Consortium, Partner Site Munich, D-80336 Munich, Germany

[3] Tech Univ Munich, Inst Clin Chem & Pathobiochem, Sch Med, Klinikum Rechts Isar, D-81675 Munich, Germany

[4] OmicScouts GmbH, D-85354 Freising Weihenstephan, Germany

[5] Tech Univ Munich, Inst Expt Canc Therapy, Sch Med, Klinikum Rechts Isar, D-80336 Munich, Germany

[6] Univ Hosp Essen, West German Canc Ctr, Dept Med Oncol, D-45147 Essen, Germany

[7] Partner Site Univ Hosp Essen, German Canc Consortium DKTK, D-45147 Essen, Germany

[8] German Ctr Infect Res DZIF, Partner Site Munich, D-81675 Munich, Germany

[9] Ctr Translat Canc Res TranslaTUM, D-81675 Munich, Germany

[10] Max Planck Inst Biochem, Dept Prote & Signal Transduct, D-82152 Martinsried, Germany

来源：

SCIENCE | 2023年 / 380卷 / 6640期

基金：

欧洲研究理事会; 欧盟地平线“2020”;

关键词：

LIPID RAFT; RECEPTOR; TRASTUZUMAB; INHIBITION; PERTUZUMAB; MECHANISM; REVEALS; TARGET; CELLS;

D O I：

10.1126/science.ade3925

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：93 / 101

页数：9

共 50 条

[21] Time-resolved detection of protein-protein interaction
Terazima, Masahide
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS, 2011, 40 : 62 - 62
[22] Multiple actions of time-resolved short-pulsed metamaterials
Castaldi, Giuseppe
Rizza, Carlo
Engheta, Nader
Galdi, Vincenzo
APPLIED PHYSICS LETTERS, 2023, 122 (02)
[23] Time-resolved quantitative proteomics implicates the core snRNP protein SmB together with SMN in neural trafficking
Prescott, Alan R.
Bales, Alexandra
James, John
Trinkle-Mulcahy, Laura
Sleeman, Judith E.
JOURNAL OF CELL SCIENCE, 2014, 127 (04) : 812 - 827
[24] Time-resolved observation of protein allosteric communication
Buchenberg, Sebastian
Sittel, Florian
Stock, Gerhard
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2017, 114 (33) : E6804 - E6811
[25] Time-resolved fluorescence - An approach in protein analysis
Villari, A
Micali, N
Fresta, M
Trusso, S
Puglisi, G
RECENT ADVANCES IN TRYPTOPHAN RESEARCH: TRYPTOPHAN AND SEROTONIN PATHWAYS, 1996, 398 : 739 - 747
[26] Recent successes in time-resolved protein crystallography
Wilmouth, RC
Clifton, IJ
Neutze, R
NATURAL PRODUCT REPORTS, 2000, 17 (06) : 527 - 533
[27] TIME-RESOLVED EXAFS APPLICABLE TO PROTEIN DYNAMICS
HUANG, HW
LIU, WH
BIOPHYSICAL JOURNAL, 1983, 41 (02) : A404 - A404
[28] TIME-RESOLVED CIRCULARLY POLARIZED PROTEIN PHOSPHORESCENCE
SCHAUERTE, JA
STEEL, DG
GAFNI, A
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (21) : 10154 - 10158
[29] Quantitative protein microarrays for time-resolved measurements of protein phosphorylation
Korf, Ulrike
Derdak, Sophia
Tresch, Achim
Henjes, Frauke
Schumacher, Sabrina
Schmidt, Christian
Hahn, Bettina
Lehmann, Wolf D.
Poustka, Annemarie
Beissbarth, Tim
Klingmueller, Ursula
PROTEOMICS, 2008, 8 (21) : 4603 - 4612
[30] A proteomics workflow for quantitative and time-resolved analysis of adaptation reactions of internalized bacteria
Pfoertner, Henrike
Wagner, Juliane
Surmann, Kristin
Hildebrandt, Petra
Ernst, Sandra
Bernhardt, Joerg
Schurmann, Claudia
Gutjahr, Melanie
Depke, Maren
Jehmlich, Ulrike
Dhople, Vishnu
Hammer, Elke
Steil, Leif
Voelker, Uwe
Schmidt, Frank
METHODS, 2013, 61 (03) : 244 - 250

← 1 2 3 4 5 →