PXD043247

PXD043247 is an original dataset announced via ProteomeXchange.

Title	The Golgi stacking protein GRASP55 is targeted by the natural compound prodigiosin
Description	The bacterial secondary metabolite prodigiosin has been shown to exert anticancer, antimalarial, antibacterial and immunomodulatory properties. With regard to cancer, it has been reported to affect cancer cells but not non-malignant cells, rendering prodigiosin a promising lead compound for anticancer drug discovery. However, a direct protein target has not yet been experimentally identified. Thus, we used mass spectrometry-based thermal proteome profiling and identified the Golgi stacking protein GRASP55 as target protein of prodigiosin. We show that prodigiosin treatment severely affects Golgi morphology and functionality, and that prodigiosin-dependent cytotoxicity is partially reduced in GRASP55 knockout cells. We also found that prodigiosin treatment results in decreased cathepsin activity and overall blocks autophagic flux, whereas co-localization of the autophagosomal marker LC3 and the lysosomal marker LAMP1 is clearly promoted. Finally, we observed that autophagosomes accumulate at GRASP55-positive structures, pointing towards an involvement of an altered Golgi function in the autophagy-inhibitory effect of this natural compound. Taken together, we propose that prodigiosin affects autophagy and Golgi apparatus integrity in an interlinked mode of action involving the regulation of organelle alkalization and the Golgi stacking protein GRASP55.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:12:37.188.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thomas Lenz
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-23 09:29:41	ID requested
1	2023-10-24 14:39:40	announced
⏵ 2	2023-11-14 09:12:38	announced	2023-11-14: Updated project metadata.

Berning L, Lenz T, Bergmann AK, Poschmann G, Brass HUC, Schl, ü, termann D, Friedrich A, Mendiburo MJ, David C, Akg, ü, n S, Pietruszka J, St, ü, hler K, Stork B, The Golgi stacking protein GRASP55 is targeted by the natural compound prodigiosin. Cell Commun Signal, 21(1):275(2023) [pubmed]

submitter keyword: Prodigiosin

Golgi apparatus

Natural Compound

Autophagy

Target Identification

Kai Stühler
contact affiliation	Molecular Proteomics Laboratory, Biological Medical Research Centre, Heinrich Heine University, 40225 Düsseldorf, Germany
contact email	kai.stuehler@hhu.de
lab head
Thomas Lenz
contact affiliation	MPL/BMFZ, HHU Düsseldorf
contact email	thomas.lenz@hhu.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/10/PXD043247

PRIDE project URI

• PRIDE
  1. PXD043247
     1. Label: PRIDE project
     2. Name: The Golgi stacking protein GRASP55 is targeted by the natural compound prodigiosin