TY  - JOUR
AU  - Zecha, Jana
AU  - Bayer, Florian P
AU  - Wiechmann, Svenja
AU  - Woortman, Julia
AU  - Berner, Nicola
AU  - Müller, Julian
AU  - Schneider, Annika
AU  - Kramer, Karl
AU  - Abril-Gil, Mar
AU  - Hopf, Thomas
AU  - Reichart, Leonie
AU  - Chen, Lin
AU  - Hansen, Fynn M
AU  - Lechner, Severin
AU  - Samaras, Patroklos
AU  - Eckert, Stephan
AU  - Lautenbacher, Ludwig
AU  - Reinecke, Maria
AU  - Hamood, Firas
AU  - Prokofeva, Polina
AU  - Vornholz, Larsen
AU  - Falcomatà, Chiara
AU  - Dorsch, Madeleine
AU  - Schröder, Ayla
AU  - Venhuizen, Anton
AU  - Wilhelm, Stephanie
AU  - Médard, Guillaume
AU  - Stoehr, Gabriele
AU  - Ruland, Jürgen
AU  - Grüner, Barbara
AU  - Saur, Dieter Karl Maximilian
AU  - Buchner, Maike
AU  - Ruprecht, Benjamin
AU  - Hahne, Hannes
AU  - The, Matthew
AU  - Wilhelm, Mathias
AU  - Kuster, Bernhard
TI  - Decrypting drug actions and protein modifications by dose- and time-resolved proteomics.
JO  - Science
VL  - 380
IS  - 6640
SN  - 0036-8075
CY  - Cambridge, Mass.
PB  - Moses King
M1  - DKFZ-2023-00554
SP  - 93-101
PY  - 2023
N1  - 2023 Apr 7;380(6640):93-101
AB  - Although most cancer drugs modulate the activities of cellular pathways by changing post-translational modifications (PTMs), surprisingly little is known regarding the extent and the time- and dose-response characteristics of drug-regulated PTMs. Here, we introduce a proteomic assay termed decryptM that quantifies drug-PTM modulation for thousands of PTMs in cells to shed light on target engagement and drug mechanism of action (MoA). 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 over-activating 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:36926954
DO  - DOI:10.1126/science.ade3925
UR  - https://inrepo02.dkfz.de/record/274352
ER  -