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

ABSTRACT: Lysine deacetylase inhibitors (KDACis) are approved for cutaneous T-cell lymphoma (CTCL) and multiple myeloma. Nevertheless, their mechanisms of action (MoA) remain elusive. 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 vehicle control and 10 increasing doses of the respective drug (from 100 pM to 30 mM). PTM-carrying and unmodified peptides were analyzed separately by liquid chromatography tandem mass spectrometry (LC-MS/MS) for peptide and protein identification and quantification. Furthermore, time-dependent experiments were carried out for Vorinostat and Panobinostat at their respective pEC50 concentrations from the cell viability data. In an independent experiment, the subcellular proteomes of Panobinostat-treated cells were measured.

INSTRUMENT(S): Orbitrap Eclipse, Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Bernhard Kuster

PROVIDER: MSV000093608 | MassIVE | Fri Dec 08 10:19:00 GMT 2023

SECONDARY ACCESSION(S): PXD047659

REPOSITORIES: MassIVE

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