Dataset - Decrypting lysine deacetylase inhibitor action and protein modifications by dose-resolved proteomics

Dataset Summary

Lysine deacetylase inhibitors (KDACis) are approved for cutaneous T-cell lymphoma (CTCL), peripheral T-cell lymphoma (PTCL), and multiple myeloma. Despite the mechanism of action(s) (MoA) remains elusive, these inhibitors lead to increasing acetylation levels of histones and other proteins, altered gene expression and cell death. To characterize the MoA of these drugs in more detail, we systematically measured dose-dependent changes in protein expression, acetylation, and phosphorylation in response to 21 clinical and pre-clinical KDACis. MV4-11 cells were treated for 6 h with 1 vehicle control and 10 increasing doses of the respective drug (from 100 pM to 30 mM). Proteins were digested with trypsin, and the resulting 11 peptide preparations corresponding to one drug dose each were encoded by stable isotopes (tandem mass tags, TMT-11plex) and combined. Acetylated peptides were subsequently enriched by immunoprecipitation and phosphopeptides by immobilized metal affinity chromatography (IMAC). PTM-carrying and unmodified peptides were analyzed separately by liquid chromatography tandem mass spectrometry (LC-MS/MS) for peptide and protein identification and quantification. Additionally, Vorinostat and Panobinostat were also recorded as time-dependent experiments at their pEC50 concentration, respectively. 

Dataset structure

Here, we provide all curve data processed with CurveCurator v0.4.0 (https://github.com/kusterlab/curve_curator). Each drug is a zip folder containing acetylome, phosphoproteome, and fullproteome data. Next to each data set is the toml parameter file used to generate the curves.txt and dashboard.html files. Time-dependent data is indicated by "td" and dose-dependent data is indicated by "dd".