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

ABSTRACT: Measuring dose-dependent effects of drugs on post-translational modifications on a proteome-wide scale reveals how these drugs work in cells. Here, we present a quantitative chemical proteomic approach termed decryptM, able to assess target and pathway engagement as well as the mode of action (MoA) of diverse cancer drugs in cells by measuring their dose- (and time-) resolved modulation of PTMs on a proteomic scale. Data collected for 31 drugs, representing six drug classes in 13 human cell lines, demonstrate that the approach is widely applicable. The body of data represents ~1.8 million quantitative cellular drug assays (dose-response curves) including 47502 regulated p-peptides (of 124660 detected on 11982 proteins), 7316 Ubi-peptides (of 9173 detected on 3006 proteins), and 546 Ac-peptides (of 2478 detected on 1377 proteins). Most PTMs were not regulated by most drugs, which is highly valuable information for understanding which pathways are addressed (or not) by each drug in cells. The decryptM data have been incorporated into ProteomicsDB and can be explored interactively. The raw files, searches, curves files, and result PDFs can be downloaded here. For details, have a look at the Experiment_summary.xlsx.Paper: doi/10.1126/science.ade3925

INSTRUMENT(S): Orbitrap Fusion Lumos, Q Exactive HF, Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Cell Type Cancer

SUBMITTER: Florian P Bayer  

LAB HEAD: Bernhard Kuster

PROVIDER: PXD037285 | Pride | 2023-03-17

REPOSITORIES: Pride