Unknown

Dataset Information

0

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

ABSTRACT: 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.

SUBMITTER: Zecha J 

PROVIDER: S-EPMC7615311 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

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

Zecha Jana J   Bayer Florian P FP   Wiechmann Svenja S   Woortman Julia J   Berner Nicola N   Müller Julian J   Schneider Annika A   Kramer Karl K   Abril-Gil Mar M   Hopf Thomas T   Reichart Leonie L   Chen Lin L   Hansen Fynn M FM   Lechner Severin S   Samaras Patroklos P   Eckert Stephan S   Lautenbacher Ludwig L   Reinecke Maria M   Hamood Firas F   Prokofeva Polina P   Vornholz Larsen L   Falcomatà Chiara C   Dorsch Madeleine M   Schröder Ayla A   Venhuizen Anton A   Wilhelm Stephanie S   Médard Guillaume G   Stoehr Gabriele G   Ruland Jürgen J   Grüner Barbara M BM   Saur Dieter D   Buchner Maike M   Ruprecht Benjamin B   Hahne Hannes H   The Matthew M   Wilhelm Mathias M   Kuster Bernhard B  

Science (New York, N.Y.) 20230316 6640

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 identify  ...[more]

Similar Datasets

Proteomics Decrypting drug actions and protein modifications by dose- and time-resolved chemical proteomics
2023-03-17 | PXD037285 | Pride
Unknown Decrypting the molecular basis of cellular drug phenotypes by dose-resolved expression proteomics.
| S-EPMC11919725 | biostudies-literature
Proteomics Decrypting lysine deacetylase inhibitor action and protein modifications by dose-resolved proteomics
2023-12-08 | MSV000093608 | MassIVE
Proteomics Decrypting the molecular basis of cellular drug phenotypes by dose-resolved expression proteomics
2023-12-13 | MSV000093659 | MassIVE
Transcriptomics Time-Resolved Proteomics Extends Ribosome Profiling-Based Measurements of Protein Synthesis Dynamics
2017-05-18 | E-GEOD-69047 | biostudies-arrayexpress
Proteomics Decrypting lysine deacetylase inhibitor action and protein modifications by dose-resolved proteomics
| PXD047419 | panorama
Transcriptomics Time-Resolved Proteomics Extends Ribosome Profiling-Based Measurements of Protein Synthesis Dynamics
2017-05-18 | GSE69047 | GEO
Unknown Time-Resolved Proteomics Extends Ribosome Profiling-Based Measurements of Protein Synthesis Dynamics.
| S-EPMC5546878 | biostudies-literature
Unknown Time-resolved proteomics of adenovirus infected cells.
| S-EPMC6155545 | biostudies-literature
Unknown Time-resolved interaction proteomics of the GIGANTEA protein under diurnal cycles in Arabidopsis.
| S-EPMC6373471 | biostudies-literature