Proteomics

Dataset Information

0

A mass spectrometry-based proteome map of drug action in lung cancer cell lines Part 3

ABSTRACT: Mass spectrometry-based discovery proteomics is an essential tool for the proximal read-out of cellular drug action. Here, we used a robust proteomic workflow to rapidly and systematically profile the proteomes of five cell lines in response to > 50 drugs. We found that aggregating millions of quantitative protein-drug associations substantially improved the mechanism of action (MoA) deconvolution of single compounds. For example, MoA specificity increased after removal of proteins which frequently responded to drugs and the aggregation of proteome changes across multiple cell lines resolved compound effects on proteostasis. These characteristics were further leveraged to demonstrate efficient target identification of protein degraders. Moreover, we followed up on selected proteomic findings and showed that the inhibition of mitochondrial function is an off-target mechanism of the clinical MEK inhibitor PD184352 and that Ceritinib, an FDA approved drug in lung cancer, modulates autophagy. Overall, this study demonstrates that large-scale proteome perturbation profiling can be a useful addition to the drug discovery toolbox.

INSTRUMENT(S): Q Exactive HF

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

SUBMITTER: An Chi  

PROVIDER: MSV000087953 | MassIVE | Fri Aug 06 18:19:00 BST 2021

SECONDARY ACCESSION(S): PXD018571

REPOSITORIES: MassIVE

Json Xml

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1
altmetric image

Publications

Mass spectrometry-based discovery proteomics is an essential tool for the proximal readout of cellular drug action. Here, we apply a robust proteomic workflow to rapidly profile the proteomes of five lung cancer cell lines in response to more than 50 drugs. Integration of millions of quantitative protein-drug associations substantially improved the mechanism of action (MoA) deconvolution of single compounds. For example, MoA specificity increased after removal of proteins that frequently respond  ...[more]

Similar Datasets

Proteomics A mass spectrometry-based proteome map of drug action in lung cancer cell lines
2020-08-17 | PXD018569 | Pride
Proteomics A mass spectrometry-based proteome map of drug action in lung cancer cell lines Part 6
2020-08-17 | PXD018574 | Pride
Proteomics A mass spectrometry-based proteome map of drug action in lung cancer cell lines Part 2
2020-08-17 | PXD018570 | Pride
Proteomics A mass spectrometry-based proteome map of drug action in lung cancer cell lines Part 4
2020-08-17 | PXD018572 | Pride
Proteomics A mass spectrometry-based proteome map of drug action in lung cancer cell lines
2020-08-17 | PXD018573 | Pride
Proteomics A mass spectrometry-based proteome map of drug action in lung cancer cell lines Part 3
2020-08-17 | PXD018571 | Pride
Proteomics A mass spectrometry-based proteome map of drug action in lung cancer cell lines
2021-08-06 | MSV000087954 | MassIVE
Proteomics A mass spectrometry-based proteome map of drug action in lung cancer cell lines Part 6
2021-08-06 | MSV000087955 | MassIVE
Proteomics A mass spectrometry-based proteome map of drug action in lung cancer cell lines
2021-08-06 | MSV000087949 | MassIVE
Proteomics A mass spectrometry-based proteome map of drug action in lung cancer cell lines Part 4
2021-08-06 | MSV000087952 | MassIVE