PXD022449

PXD022449 is an original dataset announced via ProteomeXchange.

Title	Interaction with ribosomal proteins accompanies ER stress-induction of the anticancer metallodrug BOLD-100/KP1339
Description	The ruthenium-based anticancer agent BOLD-100/KP1339 has shown promising results in several in vitro and in vivo tumour models, as well as in early clinical trials. However, its mode of action remains to be fully elucidated. Recent evidence identified ER stress-induction and concomitant down-modulation of HSPA5 (GRP78) as key drug effects. By exploiting the naturally formed adduct between BOLD-100 and human serum albumin as an immobilization strategy, we were able to perform target profiling experiments that revealed the ribosomal proteins RPL10, RPL24 and the transcription factor GTF2I as potential interactors of this ruthenium(III) anticancer agent. Integrating these findings with proteomic profiling and transcriptomic experiments supported ribosomal disturbance and concomitant induction of endoplasmic reticulum (ER) stress. The formation of poly-ribosomes and ER swelling of treated cancer cells by electron microscopy validated this finding. Thus, the direct interaction of BOLD-100 with ribosomal proteins seems to accompany ER stress-induction and modulation of GRP78 in cancer cells.
HostingRepository	PRIDE
AnnounceDate	2021-06-01
AnnouncementXML	Submission_2021-06-01_04:30:35.623.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD022449
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	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-11-10 02:00:22	ID requested
⏵ 1	2021-06-01 04:30:36	announced

Neuditschko B, Legin AA, Baier D, Schintlmeister A, Reipert S, Wagner M, Keppler BK, Berger W, Meier-Menches SM, Gerner C, Interaction with Ribosomal Proteins Accompanies Stress Induction of the Anticancer Metallodrug BOLD-100/KP1339 in the Endoplasmic Reticulum. Angew Chem Int Ed Engl, 60(10):5063-5068(2021) [pubmed]

submitter keyword: anticancer agents, KP1339, BOLD-100, proteomics, target identification

Christopher Gerner
contact affiliation	Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Str. 38, 1090 Vienna (Austria)
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. PXD022449
     1. Label: PRIDE project
     2. Name: Interaction with ribosomal proteins accompanies ER stress-induction of the anticancer metallodrug BOLD-100/KP1339