Decrypting drug actions and protein modifications by dose- and time-resolved proteomics
2023-03-16
Jana Zecha, Florian P. Bayer, Svenja Wiechmann, Julia Woortman, Nicola Berner Julian Müller, Annika Schneider, Karl Kramer, Mar Abril-Gil, Thomas Hopf, Leonie Reichart, Lin Chen, Fynn M. Hansen, Severin Lechner, Patroklos Samaras, Stephan Eckert, Ludwig Lautenbacher, Maria Reinecke, Firas Hamood1, Polina Prokofeva, Larsen Vornholz, Chiara Falcomatà, Madeleine Dorsch, Ayla Schröder, Anton Venhuizen, Stephanie Wilhelm, Guillaume Médard, Gabriele Stoehr, Jürgen Ruland, Barbara M. Grüner, Dieter Saur, Maike Buchner, Benjamin Ruprecht, Hannes Hahne, Matthew The, Mathias Wilhelm, Bernhard Kuster
J. Zecha et al., Science, 2023
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.
Speaker: Prof. Dr. Thomas Carell
Ludwig-Maximilians-Universität München
Institut für Chemische Epigenetik (ICEM)
Department of Chemistry
Office:
Würmtalstrasse 201
81377 Munich
Germany
Mailing address:
Butenandtstr. 5 - 13
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Managing Director: Dr. Oliver Baron
Institute for Chemical Epigenetics Munich (ICEM)
Ludwig-Maximilians-Universität München
Butenandtstr. 5 - 13
81377 Munich Germany
Phone: +49 (0)89 2180-77661
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Secretary: Birgit Carell
Institute for Chemical Epigenetics Munich (ICEM)
Office:
Würmtalstrasse 201, Haus L - EG / Room: 007
81377 Munich
Germany
Mailing address:
Butenandtstr. 5 - 13
81377 Munich
Germany
Phone: +49 (0)89 2180-77751
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Prof. Dr. Lena Daumann
LMU Munich
Department of Chemistry
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81377 Munich, Germany
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Dr. Sabine Schneider
LMU Munich
Institute for Chemical Epigenetics
Butenandtstr. 5 - 13
House L
81377 Munich, Germany
Phone: +49 89 2180 77716
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Dr. Martin Sumser (Coordinator)
LMU Munich
Institute for Chemical Epigenetics
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81377 Munich, Germany
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