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Zecha, Jana ;
Bayer, Florian P. ;
Wiechmann, Svenja ;
Woortman, Julia ;
Berner, Nicola ;
Müller, Julian ;
Schneider, Annika ;
Kramer, Karl ;
Abril-Gil, Mar ;
Hopf, Thomas ;
Reichart, Leonie ;
Chen, Lin ;
Hansen, Fynn M. ;
Lechner, Severin ;
Samaras, Patroklos ;
Eckert, Stephan ;
Lautenbacher, Ludwig ;
Reinecke, Maria ;
Hamood, Firas ;
Prokofeva, Polina ;
Vornholz, Larsen ;
Falcomatà, Chiara ;
Dorsch, Madeleine ;
Schröder, Ayla ;
[...]
Decrypting drug actions and protein modifications by dose- and time-resolved proteomics
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- Media type: E-Article
- Title: Decrypting drug actions and protein modifications by dose- and time-resolved proteomics
- Contributor: Zecha, Jana ; Bayer, Florian P. ; Wiechmann, Svenja ; Woortman, Julia ; Berner, Nicola ; Müller, Julian ; Schneider, Annika ; Kramer, Karl ; Abril-Gil, Mar ; Hopf, Thomas ; Reichart, Leonie ; Chen, Lin ; Hansen, Fynn M. ; Lechner, Severin ; Samaras, Patroklos ; Eckert, Stephan ; Lautenbacher, Ludwig ; Reinecke, Maria ; Hamood, Firas ; Prokofeva, Polina ; Vornholz, Larsen ; Falcomatà, Chiara ; Dorsch, Madeleine ; Schröder, Ayla ; Venhuizen, Anton ; Wilhelm, Stephanie ; Médard, Guillaume ; Stoehr, Gabriele ; Ruland, Jürgen ; Grüner, Barbara M. ; Saur, Dieter ; Buchner, Maike ; Ruprecht, Benjamin ; Hahne, Hannes ; The, Matthew ; Wilhelm, Mathias ; Kuster, Bernhard
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Published:
American Association for the Advancement of Science (AAAS), 2023
- Published in: Science, 380 (2023) 6640, Seite 93-101
- Language: English
- DOI: 10.1126/science.ade3925
- ISSN: 0036-8075; 1095-9203
- Origination:
- Footnote:
- Description: 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.