PXD009185

PXD009185 is an original dataset announced via ProteomeXchange.

Title	Systematic analysis of synergistic proteome modulations in a drug combination of cisplatin and MLN4924
Description	Chemotherapeutic treatment regimens often take advantage of synergistic effects of drug combinations. Anticipating that synergistic effects on cell biological level likely manifest on proteome level, the analysis of proteome modulations represents an appropriate strategy to study drug combinations on molecular level. More specifically, the detection of single proteins exhibiting synergistic abundance changes could be helpful to shed light on key molecules, which contribute in mechanisms facilitating the synergistic interaction and therefore represent potential target for specific therapeutic approaches. In the reported study, we investigated the drug combination of cisplatin and the neddylation inhibitor MLN4924 in HCT-116 cells via cell biological analyses and mass spectrometry-based quantitative proteomics. From 1,789 proteins quantified with two unique peptides, activated RNA polymerase II transcriptional coactivator p15 (SUB1) was highlighted as most synergistically regulated protein using a synergistic scoring approach. Western blotting and analyses of cellular processes associated with this protein (DNA damage, oxidative stress and apoptosis) revealed supporting evidence for the synergistic regulation. Whereas the distinct role of SUB1 in the investigated drug combination needs to be elucidated in future studies, the presented results demonstrated the benefit and feasibility of synergistic scoring of proteome alterations to highlight proteins that likely contribute to the underlying molecular mechanisms of synergistic effects.
HostingRepository	PRIDE
AnnounceDate	2018-10-02
AnnouncementXML	Submission_2018-10-02_05:03:54.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD009185
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Dominik Andre Meger
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	residues isobaric at 113.084064 Da; Oxidation; Carbamidomethyl
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2018-03-12 06:59:13	ID requested
⏵ 1	2018-10-02 05:03:55	announced

Megger DA, Abou-Eid S, Z, ü, lch B, Sitek B, Systematic analysis of synergistic proteome modulations in a drug combination of cisplatin and MLN4924. Mol Omics, 14(6):450-457(2018) [pubmed]

curator keyword: Biomedical

submitter keyword: Human, LC-MS/MS, Synergy

Dominik Andre Megger
contact affiliation	Ruhr-Universität Bochum Medizinisches Proteom-Center Universitätsstr. 150 D-44801 Bochum Germany
contact email	dominik.megger@rub.de
lab head
Dominik Andre Meger
contact affiliation	Medizinisches Proteom-Center (MPC), Ruhr-Universität Bochum, Germany
contact email	dominik.megger@rub.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD009185
     1. Label: PRIDE project
     2. Name: Systematic analysis of synergistic proteome modulations in a drug combination of cisplatin and MLN4924