PXD004791

PXD004791 is an original dataset announced via ProteomeXchange.

Title	Response Profiling Using Shotgun Proteomics Enables Establishing Global Metallodrug Mechanisms of Action - nuclear proteins of KP46-treated SW480 epithelial cells
Description	Response profiling using shotgun proteomics for establishing global metallodrug mechanisms of action in two colon carcinoma cell lines, HCT116 and SW480, was applied and evaluated with the clinically approved arsenic trioxide. Surprisingly, the complete established mechanism of action of arsenic trioxide was observed by protein regulations in SW480, but not in HCT116 cells. Comparing the basal protein expression in the two cell lines revealed an 80% convergence of protein identifications, but with significant expression differences, which in turn seem affect the extent of protein regulation. For example, while a clear-cut redox response was observed in SW480 cells upon arsenic treatment, such an effect was lacking in HCT116 cells and the latter express drastically higher levels of the involved redox proteins. Response profiling was then used to investigate four anticancer metallodrugs (KP46, KP772, KP1339 and KP1537) by means of functional groups of proteins and mapped their effects according to DNA repair, endocytosis, protection from oxidative stress, protection from endoplasmatic reticulum (ER) stress, cell adhesion and mitochondrial function. We were able to characterize the global effects of these metallodrugs on the proteome and generate hypotheses on hitherto unrecognized mechanisms. Significant differences in the two colon cell lines strongly suggest that knowledge of mechanistic hallmarks of anticancer metallodrug action are imperative for the design of clinical studies and that outcome may be enhanced by means of patient stratification strategies according to these hallmarks.
HostingRepository	PRIDE
AnnounceDate	2022-02-24
AnnouncementXML	Submission_2022-02-24_06:20:36.246.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD004791
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Christopher Gerner
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Oxidation; Acetyl; Carbamidomethyl
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-08-15 00:42:03	ID requested
⏵ 1	2022-02-24 06:20:37	announced

Kreutz D, Bileck A, Plessl K, Wolrab D, Groessl M, Keppler BK, Meier SM, Gerner C, Response Profiling Using Shotgun Proteomics Enables Global Metallodrug Mechanisms of Action To Be Established. Chemistry, 23(8):1881-1890(2017) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: functional protein groups, mechanism of action, metallodrug, response profiling, proteome profiling

Christopher Gerner
contact affiliation	University of Vienna, Faculty of Chemistry, Department of Analytical Chemistry
contact email	christopher.gerner@univie.ac.at
lab head
Christopher Gerner
contact affiliation	University of Vienna
contact email	christopher.gerner@univie.ac.at
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD004791
     1. Label: PRIDE project
     2. Name: Response Profiling Using Shotgun Proteomics Enables Establishing Global Metallodrug Mechanisms of Action - nuclear proteins of KP46-treated SW480 epithelial cells